]. H. Smith, C. J. Marshall-]-r, J. Roy, M. A. Yang, and . Moses, Regulation of cell signalling by uPAR, Liaudet-Coopman, M. Beaujouin, D. Derocq, M. Garcia, M. Glondu-Lassis, pp.23-36, 2008.
DOI : 10.1038/nrm2821

C. Laurent-matha, H. Prebois, F. Rochefort, B. F. Vignon-mohamed, E. Sloane et al., Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis Cysteine cathepsins: multifunctional enzymes in cancer Interaction of human breast fibroblasts with collagen I increases secretion of procathepsin B, Cancer Lett Nat Rev Cancer J Biol Chem, vol.237, issue.277, pp.167-179, 2002.

J. H. Greenbaum, M. Hager, D. Bogyo, V. Hanahan, J. A. Gocheva et al., Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis Multiple roles for cysteine cathepsins in cancer, Cysteine cathepsins and the cutting edge of cancer invasion, pp.443-453, 2004.

S. Ivanova, U. Repnik, L. Bojic, A. Petelin, V. Turk et al., Chapter Nine Lysosomes in Apoptosis, Methods Enzymol, vol.442, pp.183-199, 2008.
DOI : 10.1016/S0076-6879(08)01409-2

H. A. Chapman, Cathepsins as Transcriptional Activators?, Developmental Cell, vol.6, issue.5, pp.610-611, 2004.
DOI : 10.1016/S1534-5807(04)00141-8

M. M. Mueller and N. E. Fusenig, Tumor-stroma interactions directing phenotype and progression of epithelial skin tumor cells, Differentiation, vol.70, issue.9-10, pp.486-497, 2002.
DOI : 10.1046/j.1432-0436.2002.700903.x

N. I. Affara, P. Andreu, and L. M. Coussens, Delineating Protease Functions During ???Cancer Development, Methods Mol Biol, vol.539, pp.1-32, 2009.
DOI : 10.1007/978-1-60327-003-8_1

M. Cudic and G. B. Fields, Extracellular Proteases as Targets for Drug Development, Current Protein & Peptide Science, vol.10, issue.4, pp.297-307, 2009.
DOI : 10.2174/138920309788922207

P. Capony, H. Ferrara, and . Rochefort, Cloning and sequencing of the 52K cathepsin D complementary deoxyribonucleic acid of MCF7 breast cancer cells and mapping on chromosome 11, Mol Endocrinol, vol.2, pp.186-192, 1988.

A. M. Samarel, A. G. Ferguson, R. S. Decker, and M. Lesch, Effects of cysteine protease inhibitors on rabbit cathepsin D maturation, Am J Physiol, vol.257, pp.1069-1079, 1989.

V. Gieselmann, A. Hasilik, and K. Figura, Processing of human cathepsin D in lysosomes in vitro, J Biol Chem, vol.260, pp.3215-3220, 1985.

V. Laurent-matha, D. Derocq, C. Prebois, N. Katunuma, and E. Liaudet-coopman, Processing of Human Cathepsin D Is Independent of Its Catalytic Function and Auto-Activation: Involvement of Cathepsins L and B, Journal of Biochemistry, vol.139, issue.3, pp.363-371, 2006.
DOI : 10.1093/jb/mvj037
URL : https://hal.archives-ouvertes.fr/inserm-00153742

. Olsen, Neuronal loss and brain atrophy in mice lacking cathepsins B and L, Proc Natl Acad Sci U S A, vol.99, pp.7883-7888, 2002.

A. Wille, A. Gerber, A. Heimburg, A. Reisenauer, C. Peters et al., Cathepsin L is involved in cathepsin D processing and regulation of apoptosis in A549 human lung epithelial cells, Biological Chemistry, vol.385, issue.7, pp.385-665, 2004.
DOI : 10.1515/BC.2004.082

P. Metcalf and M. Fusek, Two crystal structures for cathepsin D: the lysosomal targeting signal and active site, Embo J, vol.12, pp.1293-1302, 1993.

A. M. Collins, J. W. Silva, and . Erickson, Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design, Proc Natl Acad Sci, pp.90-6796, 1993.

A. Y. Lee, S. V. Gulnik, and J. W. Erickson, Conformational switching in an aspartic proteinase, Nature Structural Biology, vol.64, issue.10, pp.866-871, 1998.
DOI : 10.1107/S0021889891007240

V. Cavailles, P. Augereau, M. Garcia, and H. Rochefort, Estrogens and growth factors induce the mRNA of the 52K-pro-cathepsin-D secreted by breast cancer cells, Nucleic Acids Research, vol.16, issue.5, pp.1903-1919, 1988.
DOI : 10.1093/nar/16.5.1903

. Richard-foy, Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines, Oncogene, vol.18, pp.533-541, 1999.

F. Capony, C. Rougeot, P. Montcourrier, V. Cavailles, G. Salazar et al., Increased secretion, altered processing, and glycosylation of pro-cathepsin D in human mammary cancer cells, Cancer Res, pp.49-3904, 1989.

R. Castino, S. Delpal, E. Bouguyon, M. Demoz, C. Isidoro et al., Prolactin Promotes the Secretion of Active Cathepsin D at the Basal Side of Rat Mammary Acini, Endocrinology, vol.149, issue.8, pp.4095-4105, 2008.
DOI : 10.1210/en.2008-0249

V. Laurent-matha, M. R. Farnoud, A. Lucas, C. Rougeot, M. Garcia et al., Endocytosis of pro-cathepsin D into breast cancer cells is mostly independent of mannose-6- phosphate receptors, J Cell Sci, vol.111, pp.2539-2549, 1998.

F. Capony, T. Braulke, C. Rougeot, S. Roux, P. Montcourrier et al., Specific Mannose-6-Phosphate Receptor-Independent Sorting of Pro-Cathepsin D in Breast Cancer Cells, Experimental Cell Research, vol.215, issue.1, pp.154-163, 1994.
DOI : 10.1006/excr.1994.1327

V. Laurent-matha, A. Lucas, S. Huttler, K. Sandhoff, M. Garcia et al., Procathepsin D Interacts with Prosaposin in Cancer Cells but Its Internalization Is Not Mediated by LDL Receptor-Related Protein, Experimental Cell Research, vol.277, issue.2, pp.210-219, 2002.
DOI : 10.1006/excr.2002.5556

M. Canuel, A. Korkidakis, K. Konnyu, and C. R. Morales, Sortilin mediates the lysosomal targeting of cathepsins D and H, Biochemical and Biophysical Research Communications, vol.373, issue.2, pp.292-297, 2008.
DOI : 10.1016/j.bbrc.2008.06.021

. Yonezawa, Development-dependent expression of cathepsins d and e in various rat tissues, with special reference to the high expression of cathepsin e in fetal liver, Zoolog Sci, vol.15, pp.517-523, 1998.

M. Hess, K. Evers, and . Figura, Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells, Embo J, pp.14-3599, 1995.

M. Koike, H. Nakanishi, P. Saftig, J. Ezaki, K. Isahara et al., Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons, Neuroscience Research, vol.38, pp.6898-6906, 2000.
DOI : 10.1016/S0168-0102(00)81020-2

E. Momoi, C. Kominami, K. Peters, P. Figura, Y. Saftig et al., Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice, Mol Cell Neurosci, vol.22, pp.146-161, 2003.

K. C. Walls, B. J. Klocke, P. Saftig, M. Shibata, Y. Uchiyama et al., Altered Regulation of Phosphatidylinositol 3-kinase Signaling in Cathepsin D-Deficient Brain, Autophagy, vol.3, issue.3, pp.222-229, 2007.
DOI : 10.4161/auto.3822

L. Myllykangas, J. Tyynela, A. Page-mccaw, G. M. Rubin, M. J. Haltia et al., Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses, Neurobiology of Disease, vol.19, issue.1-2, pp.194-199, 2005.
DOI : 10.1016/j.nbd.2004.12.019

J. Tyynela, I. Sohar, D. E. Sleat, R. M. Gin, R. J. Donnelly et al., A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration, The EMBO Journal, vol.19, issue.12, pp.19-2786, 2000.
DOI : 10.1093/emboj/19.12.2786

T. Awano, M. L. Katz, D. P. O-'brien, J. F. Taylor, J. Evans et al., A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis, Molecular Genetics and Metabolism, vol.87, issue.4, pp.341-348, 2006.
DOI : 10.1016/j.ymgme.2005.11.005

J. Lehesjoki and . Tyynela, Cathepsin D deficiency underlies congenital human neuronal ceroidlipofuscinosis, Brain, vol.129, pp.1438-1445, 2006.

J. Saftig and . Gartner, Cathepsin D deficiency is associated with a human neurodegenerative disorder, Am J Hum Genet, vol.78, pp.988-998, 2006.

J. Tyynela, I. Sohar, D. E. Sleat, R. M. Gin, R. J. Donnelly et al., Congenital ovine neuronal ceroid lipofuscinosis ??? acathepsin D deficiency with increased levels of the inactive enzyme, European Journal of Paediatric Neurology, vol.5, pp.43-45, 2001.
DOI : 10.1053/ejpn.2000.0433

J. M. Tennison, S. Booker, S. Koch, K. Partanen, J. Suzuki et al., Novel mutation and the first prenatal screening of cathepsin D deficiency (CLN10), Acta Neuropathol, vol.117, pp.201-208, 2009.

J. Saftig, M. B. Woulfe, L. Feany, M. G. Myllykangas, J. Schlossmacher et al., Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo, Mol Brain, vol.2, issue.5, 2009.

R. Heusch, A. Schulz, H. Hilfiker, and . Drexler, A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy, Cell, vol.128, pp.589-600, 2007.

A. M. Sheikh, X. Li, G. Wen, Z. Tauqeer, W. T. Brown et al., Cathepsin D and apoptosis related proteins are elevated in the brain of autistic subjects, Neuroscience, vol.165, issue.2, pp.363-370, 2010.
DOI : 10.1016/j.neuroscience.2009.10.035

O. Vasiljeva and B. Turk, Dual contrasting roles of cysteine cathepsins in cancer progression: Apoptosis versus tumour invasion, Biochimie, vol.90, issue.2, pp.380-386, 2008.
DOI : 10.1016/j.biochi.2007.10.004

A. Minarowska, L. Minarowski, A. Karwowska, and M. Gacko, Regulatory role of cathepsin D in apoptosis, Folia Histochem Cytobiol, vol.45, pp.159-163, 2007.

V. Zuzarte-luis, J. A. Montero, N. Torre-perez, J. A. Garcia-porrero, and J. M. Hurle, Cathepsin D gene expression outlines the areas of physiological cell death during embryonic development, Developmental Dynamics, vol.301, issue.3, pp.236-880, 2007.
DOI : 10.1002/dvdy.21076

G. Berchem, M. Glondu, M. Gleizes, J. P. Brouillet, F. Vignon et al., Cathepsin-D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis, Oncogene, vol.21, issue.38, pp.5951-5955, 2002.
DOI : 10.1038/sj.onc.1205745

V. Sagulenko, D. Muth, E. Sagulenko, T. Paffhausen, M. Schwab et al., Cathepsin D protects human neuroblastoma cells from doxorubicin-induced cell death, Carcinogenesis, vol.29, issue.10, pp.1869-1877, 2008.
DOI : 10.1093/carcin/bgn147

L. P. Deiss, H. Galinka, H. Berissi, O. Cohen, and A. Kimchi, Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha, Embo J, pp.15-3861, 1996.

K. Ollinger, Inhibition of Cathepsin D Prevents Free-Radical-Induced Apoptosis in Rat Cardiomyocytes, Archives of Biochemistry and Biophysics, vol.373, issue.2, pp.346-351, 2000.
DOI : 10.1006/abbi.1999.1567

K. Kagedal, U. Johansson, and K. Ollinger, The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress, The FASEB Journal, vol.15, pp.1592-1594, 2001.
DOI : 10.1096/fj.00-0708fje

K. Roberg and K. Ollinger, Oxidative stress causes relocation of the lysosomal enzyme cathepsin D with ensuing apoptosis in neonatal rat cardiomyocytes, Am J Pathol, vol.152, pp.1151-1156, 1998.

K. Takuma, M. Kiriu, K. Mori, E. Lee, R. Enomoto et al., Roles of cathepsins in reperfusion-induced apoptosis in cultured astrocytes, Neurochemistry International, vol.42, issue.2, pp.42-153, 2003.
DOI : 10.1016/S0197-0186(02)00077-3

A. C. Johansson, H. Steen, K. Ollinger, and K. Roberg, Cathepsin D mediates cytochrome c release and caspase activation in human fibroblast apoptosis induced by staurosporine, Cell Death and Differentiation, vol.10, issue.11, pp.1253-1259, 2003.
DOI : 10.1038/sj.cdd.4401290

M. Beaujouin, S. Baghdiguian, M. Glondu-lassis, G. Berchem, and E. Liaudet-coopman, Overexpression of both catalytically active and -inactive cathepsin D by cancer cells enhances apoptosis-dependent chemo-sensitivity, Oncogene, vol.16, issue.13, pp.1967-1973, 2006.
DOI : 10.1038/sj.onc.1209221
URL : https://hal.archives-ouvertes.fr/inserm-00153749

Y. Gan, X. Zhao, J. Hu, Z. G. Wang, and X. T. Zhao, HCCS1 overexpression induces apoptosis via cathepsin D and intracellular calcium, and HCCS1 disruption in mice causes placental abnormality, Cell Death and Differentiation, vol.28, issue.9, pp.1481-1490, 2008.
DOI : 10.1038/cdd.2008.73

. Endo, Translocation of lysosomal cathepsin D caused by oxidative stress or proteasome inhibition in primary cultured neurons and astrocytes, Biol Pharm Bull, vol.33, pp.22-28, 2010.

K. Roberg, K. Kagedal, and K. Ollinger, Microinjection of Cathepsin D Induces Caspase-Dependent Apoptosis in Fibroblasts, The American Journal of Pathology, vol.161, issue.1, pp.89-96, 2002.
DOI : 10.1016/S0002-9440(10)64160-0

K. Roberg, U. Johansson, and K. Ollinger, Lysosomal release of Cathepsin D precedes relocation of Cytochrome C and loss of mitochondrial transmembrane potential during apoptosis induced by oxidative stress, Free Radical Biology and Medicine, vol.27, issue.11-12, pp.1228-1237, 1999.
DOI : 10.1016/S0891-5849(99)00146-X

W. Wickel, A. Schneider-brachert, A. Trauzold, S. Hethke, and . Schutze, Cathepsin D links TNFinduced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation, Cell Death Differ, vol.11, pp.550-563, 2004.

R. Blomgran, L. Zheng, and O. Stendahl, Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization, Journal of Leukocyte Biology, vol.81, issue.5, pp.1213-1223, 2007.
DOI : 10.1189/jlb.0506359

N. Bidere, H. K. Lorenzo, S. Carmona, M. Laforge, F. Harper et al., Cathepsin D Triggers Bax Activation, Resulting in Selective Apoptosis-inducing Factor (AIF) Relocation in T Lymphocytes Entering the Early Commitment Phase to Apoptosis, Journal of Biological Chemistry, vol.278, issue.33, pp.31401-31411, 2003.
DOI : 10.1074/jbc.M301911200

S. Conus, R. Perozzo, T. Reinheckel, C. Peters, L. Scapozza et al., Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation, The Journal of Experimental Medicine, vol.14, issue.3, pp.685-698, 2008.
DOI : 10.1038/ncb1482

S. Zhao, E. R. Aviles, J. , and D. G. Fujikawa, Nuclear translocation of mitochondrial cytochrome c, lysosomal cathepsins B and D, and three other death-promoting proteins within the first 60 minutes of generalized seizures, Journal of Neuroscience Research, vol.90, 2010.
DOI : 10.1002/jnr.22338

N. Grdovic, M. Vidakovic, M. Mihailovic, S. Dinic, A. Uskokovic et al., Proteolytic events in cryonecrotic cell death: Proteolytic activation of endonuclease P23, Cryobiology, vol.60, issue.3, 2010.
DOI : 10.1016/j.cryobiol.2010.01.005

M. Demoz, R. Castino, P. Cesaro, F. M. Baccino, G. Bonelli et al., Endosomallysosomal proteolysis mediates death signalling by TNFalpha, not by etoposide, in L929 fibrosarcoma cells: evidence for an active role of cathepsin D, Biol Chem, pp.383-1237, 2002.

S. Watanabe, K. Ebisu, E. Ishido, Y. Kominami, and . Uchiyama, Participation of cathepsins B and D in apoptosis of PC12 cells following serum deprivation, Biochem Biophys Res Commun, vol.251, pp.199-203, 1998.

C. Tardy, J. Tyynela, A. Hasilik, T. Levade, and N. , Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D, Cell Death and Differentiation, vol.10, issue.9, pp.1090-1100, 2003.
DOI : 10.1038/sj.cdd.4401272

O. Schestkowa, D. Geisel, R. Jacob, and A. Hasilik, The catalytically inactive precursor of cathepsin D induces apoptosis in human fibroblasts and HeLa cells, Journal of Cellular Biochemistry, vol.281, issue.6, pp.1558-1566, 2007.
DOI : 10.1002/jcb.21269

B. R. Westley and F. E. May, Prognostic value of cathepsin D in breast cancer, British Journal of Cancer, vol.20, issue.2, pp.189-190, 1999.
DOI : 10.1038/sj.bjc.6690032

G. Ferrandina, G. Scambia, F. Bardelli, P. Benedetti-panici, S. Mancuso et al., Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis, British Journal of Cancer, vol.76, issue.5, pp.661-666, 1997.
DOI : 10.1038/bjc.1997.442

J. A. Foekens, M. P. Look, J. Bolt-de-vries, M. E. Meijer-van-gelder, W. L. Van-putten et al., Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients, British Journal of Cancer, vol.32, issue.2, pp.300-307, 1999.
DOI : 10.1038/sj.bjc.6690048

. Schnitt, Prognostic factors in breast cancer College of American Pathologists Consensus Statement, Arch Pathol Lab Med, vol.124, pp.966-978, 1999.

M. Graeff and . Schmitt, Long-term follow-up confirms prognostic impact of PAI-1 and cathepsin D and L in primary breast cancer, Int J Biol Markers, vol.15, pp.79-83, 2000.

S. Greco, S. Marsigliante, G. Leo, and C. Storelli, Co-expression of thymidine kinase and cathepsin D in 200 primary breast carcinomas, Cancer Letters, vol.160, issue.1, pp.13-19, 2000.
DOI : 10.1016/S0304-3835(00)00550-4

Z. Gaci, M. H. Bouin-pineau, M. Gaci, A. Daban, P. Ingrand et al., Prognostic impact of cathepsin D and c-erbB-2 oncoprotein in a subgroup of node-negative breast cancer patients with low histological grade tumors, International Journal of Oncology, vol.18, pp.793-800, 2001.
DOI : 10.3892/ijo.18.4.793

P. M. Awada, L. Mathevet, Y. Berrerd, J. Barbier, and . Esteve, Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer, Breast Cancer Res Treat, vol.82, pp.47-59, 2003.
URL : https://hal.archives-ouvertes.fr/hal-00427497

L. Stackhouse, I. Wilkins, P. Evans, K. Berry, E. Rimmer et al., Prognostic markers in node-negative breast cancer: a prospective study, Cytometry B Clin Cytom, vol.59, pp.24-31, 2004.

M. Alvarez, L. Allende, M. Gonzalez, M. Sanchez, J. Vijande et al., Clinical significance of cathepsin D concentration in tumor cytosol of primary breast cancer, Int J Biol Markers, vol.20, pp.103-111, 2005.

J. T. Anim, B. John, S. S. Abdulsathar, A. Prasad, T. Saji et al., Relationship between the expression of various markers and prognostic factors in breast cancer, Acta Histochemica, vol.107, issue.2, pp.87-93, 2005.
DOI : 10.1016/j.acthis.2005.01.002

A. L. Cheng, W. G. Huang, Z. C. Chen, P. F. Zhang, M. Y. Li et al., Identificating Cathepsin D as a Biomarker for Differentiation and Prognosis of Nasopharyngeal Carcinoma by Laser Capture Microdissection and Proteomic Analysis, Journal of Proteome Research, vol.7, issue.6, pp.2415-2426, 2008.
DOI : 10.1021/pr7008548

D. Cartledge, P. J. Thompson, R. E. Selby, and . Banks, Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma, Br J Cancer, vol.101, pp.1175-1182, 2009.

P. Roger, P. Montcourrier, T. Maudelonde, J. P. Brouillet, A. Pages et al., Cathepsin D immunostaining in paraffin-embedded breast cancer cells and macrophages: Correlation with cytosolic assay, Human Pathology, vol.25, issue.9, pp.25-863, 1994.
DOI : 10.1016/0046-8177(94)90004-3

J. P. Brouillet, F. Dufour, G. Lemamy, M. Garcia, N. Schlup et al., Increased cathepsin D level in the serum of patients with metastatic breast carcinoma detected with a specific pro-cathepsin D immunoassay, Cancer, vol.49, issue.11, pp.2132-2136, 1997.
DOI : 10.1002/(SICI)1097-0142(19970601)79:11<2132::AID-CNCR10>3.0.CO;2-X

. Zwierz, Cathepsin D and carcino-embryonic antigen in serum, urine and tissues of colon adenocarcinoma patients, Hepatogastroenterology, vol.55, pp.388-393, 2008.

A. Zwierz and . Krupkowska, Activity of cathepsin D in the blood serum and urine of patients with cancer of the stomach, pancreas and liver], Pol Arch Med Wewn, vol.116, pp.1150-1154, 2006.

I. Selicharova, M. Sanda, J. Mladkova, S. S. Ohri, A. Vashishta et al., Vetvicka, 2-DE analysis of breast cancer cell lines 1833 and 4175 with distinct metastatic organ-specific potentials: comparison with parental cell line MDA-MB-231, Oncol Rep, vol.19, pp.1237-1244, 2008.

G. Baldus, A. P. Patsos, C. Corfield, F. G. Paraskeva, and . Hanisch, Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma, Proteomics, vol.10, pp.194-202, 2010.

F. Vignon, F. Capony, M. Chambon, G. Freiss, M. Garcia et al., Autocrine Growth Stimulation of the MCF 7 Breast Cancer Cells by the Estrogen-Regulated 52 K Protein*, Endocrinology, vol.118, issue.4, pp.1537-1545, 1986.
DOI : 10.1210/endo-118-4-1537

M. Garcia, D. Derocq, P. Pujol, and H. Rochefort, Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency, Oncogene, vol.5, pp.1809-1814, 1990.

M. Fusek and V. Vetvicka, Mitogenic function of human procathepsin D: the role of the propeptide, Biochemical Journal, vol.303, issue.3, pp.775-780, 1994.
DOI : 10.1042/bj3030775

V. Vetvicka, J. Vektvickova, and M. Fusek, Effect of human procathepsin D on proliferation of human cell lines, Cancer Letters, vol.79, issue.2, pp.131-135, 1994.
DOI : 10.1016/0304-3835(94)90251-8

E. Liaudet, D. Derocq, H. Rochefort, and M. Garcia, Transfected cathepsin D stimulates high density cancer cell growth by inactivating secreted growth inhibitors, Cell Growth Differ, vol.6, pp.1045-1052, 1995.

S. S. Ohri, A. Vashishta, M. Proctor, M. Fusek, and V. Vetvicka, Depletion of procathepsin D gene expression by RNA interference ??? A potential therapeutic target for breast cancer, Cancer Biology & Therapy, vol.6, issue.7, pp.1081-1087, 2007.
DOI : 10.4161/cbt.6.7.4325

S. S. Ohri, A. Vashishta, M. Proctor, M. Fusek, and V. Vetvicka, The propeptide of cathepsin D increases proliferation, invasion and metastasis of breast cancer cells, International Journal of Oncology, vol.32, pp.491-498, 2008.
DOI : 10.3892/ijo.32.2.491

E. Liaudet, M. Garcia, and H. Rochefort, Cathepsin D maturation and its stimulatory effect on metastasis are prevented by addition of KDEL retention signal, Oncogene, vol.9, pp.1145-1154, 1994.

M. Glondu, E. Liaudet-coopman, D. Derocq, N. Platet, H. Rochefort et al., Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells, Oncogene, vol.21, issue.33, pp.5127-5134, 2002.
DOI : 10.1038/sj.onc.1205657

A. Vashishta, S. S. Ohri, M. Proctor, M. Fusek, and V. Vetvicka, Ribozyme-targeting procathepsin D and its effect on invasion and growth of breast cancer cells: An implication in breast cancer therapy, International Journal of Oncology, vol.30, pp.1223-1230, 2007.
DOI : 10.3892/ijo.30.5.1223

. Coopman, A mutated cathepsin-D devoid of its catalytic activity stimulates the growth of cancer cells, Oncogene, vol.20, pp.6920-6929, 2001.

V. Vetvicka, J. Vetvickova, and M. Fusek, Effect of procathepsin D and its activation peptide on prostate cancer cells, Cancer Letters, vol.129, issue.1, pp.55-59, 1998.
DOI : 10.1016/S0304-3835(98)00091-3

V. Vetvicka, J. Vetvickova, and P. Benes, Role of enzymatically inactive procathepsin D in lung cancer, Anticancer Res, vol.24, pp.2739-2743, 2004.

. Garcia, Heat shock cognate 70 protein secretion as a new growth arrest signal for cancer cells, Oncogene, vol.29, pp.117-127, 2010.
URL : https://hal.archives-ouvertes.fr/inserm-00431120

M. Mathieu, H. Rochefort, B. Barenton, C. Prebois, and F. Vignon, Interactions of cathepsin-D and insulin-like growth factor-II (IGF-II) on the IGF-II/mannose-6-phosphate receptor in human breast cancer cells and possible consequences on mitogenic activity of IGF-II, Mol Endocrinol, pp.4-1327, 1990.

J. S. Faridi, S. Mohan, and D. D. De-leon, Modulation of Cathepsin D Routing by IGF-II Involves IGF-II Binding to IGF-II/M6P Receptor in MCF-7 Breast Cancer Cells, Growth Factors, vol.22, issue.3, pp.22-169, 2004.
DOI : 10.1080/08977190410001725531

V. Vetvicka, P. Benes, and M. Fusek, Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors, Cancer Gene Therapy, vol.9, issue.10, pp.854-863, 2002.
DOI : 10.1038/sj.cgt.7700508

V. Vetvicka, J. Vetvickova, and M. Fusek, Anti???human procathepsin D activation peptide antibodies inhibit breast cancer development, Breast Cancer Research and Treatment, vol.264, issue.3, pp.261-269, 1999.
DOI : 10.1023/A:1006238003772

A. Vashishta, S. S. Ohri, M. Proctor, M. Fusek, and V. Vetvicka, Role of activation peptide of procathepsin D in proliferation and invasion of lung cancer cells, Anticancer Res, vol.26, pp.4163-4170, 2006.

P. Briozzo, J. Badet, F. Capony, I. Pieri, P. Montcourrier et al., MCF7 mammary cancer cells respond to bFGF and internalize it following its release from extracellular matrix: A permissive role of cathepsin D, Experimental Cell Research, vol.194, issue.2, pp.252-259, 1991.
DOI : 10.1016/0014-4827(91)90362-X

J. R. Griffiths, Are cancer cells acidic?, British Journal of Cancer, vol.64, issue.3, pp.425-427, 1991.
DOI : 10.1038/bjc.1991.326

H. Rochefort and E. Liaudet-coopman, Cathepsin D in cancer metastasis: A protease and a ligand, APMIS, vol.57, issue.1-6, pp.86-95, 1999.
DOI : 10.1111/j.1699-0463.1999.tb01530.x

M. M. Mueller and N. E. Fusenig, Friends or foes ??? bipolar effects of the tumour stroma in cancer, Nature Reviews Cancer, vol.22, issue.11, pp.839-849, 2004.
DOI : 10.1038/nrc1477

L. A. Liotta and E. C. Kohn, The microenvironment of the tumour-host interface, Nature, vol.411, issue.6835, pp.375-379, 2001.
DOI : 10.1038/35077241

M. Kebers, A. Lemeur, J. M. Dierich, P. Foidart, M. C. Basset et al., In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy, J Cell Biol, vol.140, pp.1535-1541, 1998.

G. Loncarek, F. Freiss, E. Vignon, and . Liaudet-coopman, Catalytically inactive human cathepsin D triggers fibroblast invasive growth, J Cell Biol, vol.168, pp.489-499, 2005.
URL : https://hal.archives-ouvertes.fr/inserm-00153783

N. Heylen, L. M. Vincent, V. Devos, V. Dubois, C. Remacle et al., Fibroblasts capture cathepsin D secreted by breast cancer cells: Possible role in the regulation of the invasive process, International Journal of Oncology, vol.20, pp.761-767, 2002.
DOI : 10.3892/ijo.20.4.761

L. Hu, J. M. Roth, P. Brooks, J. Luty, and S. Karpatkin, Thrombin Up-regulates Cathepsin D which Enhances Angiogenesis, Growth, and Metastasis, Cancer Research, vol.68, issue.12, pp.4666-4673, 2008.
DOI : 10.1158/0008-5472.CAN-07-6276

M. Wolf, I. Clark-lewis, C. Buri, H. Langen, M. Lis et al., Cathepsin D Specifically Cleaves the Chemokines Macrophage Inflammatory Protein-1??, Macrophage Inflammatory Protein-1??, and SLC That Are Expressed in Human Breast Cancer, The American Journal of Pathology, vol.162, issue.4, pp.1183-1190, 2003.
DOI : 10.1016/S0002-9440(10)63914-4

K. Strotmann and . Spanel-borowski, Inflammatory cytokines increase extracellular procathepsin D in permanent and primary endothelial cell cultures, Eur J Cell Biol, vol.87, pp.311-323, 2008.

B. Goulet, A. Baruch, N. S. Moon, M. Poirier, L. L. Sansregret et al., A Cathepsin L Isoform that Is Devoid of a Signal Peptide Localizes to the Nucleus in S Phase and Processes the CDP/Cux Transcription Factor, Molecular Cell, vol.14, issue.2, pp.14-207, 2004.
DOI : 10.1016/S1097-2765(04)00209-6

G. Maubach, M. C. Lim, and L. Zhuo, Nuclear Cathepsin F Regulates Activation Markers in Rat Hepatic Stellate Cells, Molecular Biology of the Cell, vol.19, issue.10, pp.4238-4248, 2008.
DOI : 10.1091/mbc.E08-03-0291

E. M. Duncan, T. L. Muratore-schroeder, R. G. Cook, B. A. Garcia, J. Shabanowitz et al., Cathepsin L Proteolytically Processes Histone H3 During Mouse Embryonic Stem Cell??Differentiation, Cell, vol.135, issue.2, pp.284-294, 2008.
DOI : 10.1016/j.cell.2008.09.055
URL : http://doi.org/10.1016/j.cell.2008.09.055

E. Nepveu, B. Zerovnik, N. Turk, and . Kopitar-jerala, Stefin B interacts with histones and cathepsin L in the nucleus, J Biol Chem, vol.285, pp.10078-10086, 2010.

B. Goulet, L. Sansregret, L. Leduy, M. Bogyo, E. Weber et al., Increased Expression and Activity of Nuclear Cathepsin L in Cancer Cells Suggests a Novel Mechanism of Cell Transformation, Molecular Cancer Research, vol.5, issue.9, pp.899-907, 2007.
DOI : 10.1158/1541-7786.MCR-07-0160

H. Sheahan, J. O. Mulcahy, and . Sullivan, Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer, Int J Cancer, vol.125, pp.54-61, 2009.

C. Dash, A. Kulkarni, B. Dunn, and M. Rao, Aspartic Peptidase Inhibitors: Implications in Drug Development, Critical Reviews in Biochemistry and Molecular Biology, vol.38, issue.2, pp.89-119, 2003.
DOI : 10.1080/713609213

G. Riccioni, N. Vitulano, N. D. Orazio, and F. Bellocci, Aliskiren, the first approved renin inhibitor: Clinical application and safety in the treatment of hypertension, Advances in Therapy, vol.4, issue.SupplS-b, pp.700-710, 2009.
DOI : 10.1007/s12325-009-0050-5

C. Bjorklund, S. Oscarson, K. Benkestock, N. Borkakoti, K. Jansson et al., Design and Synthesis of Potent and Selective BACE-1 Inhibitors, Journal of Medicinal Chemistry, vol.53, issue.4, pp.1458-1464, 2010.
DOI : 10.1021/jm901168f

P. O. Johansson, Y. Chen, A. K. Belfrage, M. J. Blackman, I. Kvarnstrom et al., Design and Synthesis of Potent Inhibitors of the Malaria Aspartyl Proteases Plasmepsin I and II. Use of Solid-Phase Synthesis to Explore Novel Statine Motifs, Journal of Medicinal Chemistry, vol.47, issue.13, pp.3353-3366, 2004.
DOI : 10.1021/jm031106i

E. Lefebvre and C. A. Schiffer, Resilience to resistance of HIV-1 protease inhibitors: profile of darunavir, AIDS Rev, vol.10, pp.131-142, 2008.

K. E. Estes, S. R. Penzak, K. A. Calis, and T. J. Walsh, Pharmacology and Antifungal Properties of Anidulafungin, a New Echinocandin, Pharmacotherapy, vol.12, issue.1, pp.17-30, 2009.
DOI : 10.1177/0091270005281234

S. L. Gonias and S. V. Pizzo, Conformation and protease binding activity of binary and ternary human alpha 2-macroglobulin-protease complexes, J Biol Chem, vol.258, pp.14682-14685, 1983.

A. J. Barrett and P. M. Starkey, The interaction of alpha 2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism, Biochem J, pp.133-709, 1973.

M. Gacko, A. Minarowska, A. Karwowska, and L. Minarowski, Cathepsin D inhibitors, Folia Histochem Cytobiol, vol.45, pp.291-313, 2007.

A. Minarowska, A. Karwowska, and M. Gacko, Quantitative determination and localization of cathepsin D and its inhibitors., Folia Histochemica et Cytobiologica, vol.47, issue.2, pp.153-177, 2009.
DOI : 10.2478/v10042-009-0073-4

. Ellman, Structure-based design and combinatorial chemistry yield low nanomolar inhibitors of cathepsin D, Chem Biol, vol.4, pp.297-307, 1997.

J. A. Ellman, Combinatorial Methods to Engineer Small Molecules for Functional Genomics, Ernst Schering Res Found Workshop, pp.183-204, 2000.
DOI : 10.1007/978-3-662-04042-3_6

X. Bi, T. S. Haque, J. Zhou, A. G. Skillman, B. Lin et al., Novel Cathepsin D Inhibitors Block the Formation of Hyperphosphorylated Tau Fragments in Hippocampus, Journal of Neurochemistry, vol.157, issue.4, pp.74-1469, 2000.
DOI : 10.1046/j.1471-4159.2000.0741469.x

W. J. Wood, A. W. Patterson, H. Tsuruoka, R. K. Jain, and J. A. Ellman, Substrate Activity Screening:?? A Fragment-Based Method for the Rapid Identification of Nonpeptidic Protease Inhibitors, Journal of the American Chemical Society, vol.127, issue.44, pp.15521-15527, 2005.
DOI : 10.1021/ja0547230

A. S. Khanuja and . Negi, Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors, Bioorg Med Chem Lett, vol.16, pp.4603-4608, 2006.

M. Fusek, M. Mares, J. Vagner, Z. Voburka, and M. Baudys, Inhibition of aspartic proteinases by propart peptides of human procathepsin D and chicken pepsinogen, FEBS Letters, vol.23, issue.1-2, pp.160-162, 1991.
DOI : 10.1016/0014-5793(91)80040-A

C. G. Knight and A. J. Barrett, Interaction of human cathepsin D with the inhibitor pepstatin, Biochemical Journal, vol.155, issue.1, pp.117-125, 1976.
DOI : 10.1042/bj1550117

F. M. Tumminello, G. Leto, N. Gebbia, L. Rausa, and R. J. Bernacki, Evaluation of antitumor and antimetastatic activity of pepstatin A in some experimental tumor models, J Chemother, vol.1, pp.1135-1138, 1989.

D. Lelievre and . Scherman, Inhibition of cathepsin D by tripeptides containing statine analogs, Biochem Pharmacol, vol.58, pp.329-333, 1999.

P. Lison, I. Rodrigo, and V. Conejero, A Novel Function for the Cathepsin D Inhibitor in Tomato, PLANT PHYSIOLOGY, vol.142, issue.3, pp.1329-1339, 2006.
DOI : 10.1104/pp.106.086587

S. A. Cater, W. E. Lees, J. Hill, J. Brzin, J. Kay et al., Aspartic proteinase inhibitors from tomato and potato are more potent against yeast proteinase A than cathepsin D, Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, vol.1596, issue.1, pp.1596-76, 2002.
DOI : 10.1016/S0167-4838(02)00206-6

B. Lenarcic and V. Turk, Thyroglobulin Type-1 Domains in Equistatin Inhibit Both Papain-like Cysteine Proteinases and Cathepsin D, Journal of Biological Chemistry, vol.274, issue.2, pp.563-566, 1999.
DOI : 10.1074/jbc.274.2.563

. Jongsma, Equistatin, a protease inhibitor from the sea anemone actinia equina, is composed of three structural and functional domains, Biochem Biophys Res Commun, vol.269, pp.732-736, 2000.

M. Shibata, M. Koike, S. Waguri, G. Zhang, T. Koga et al., Cathepsin D is specifically inhibited by deoxyribonucleic acids, FEBS Letters, vol.7, issue.1-3, pp.281-284, 2002.
DOI : 10.1016/S0014-5793(02)02569-3

V. Vetvicka, J. Vetvickova, I. Hilgert, Z. Voburka, and M. Fusek, Analysis of the interaction of procathepsin D activation peptide with breast cancer cells, International Journal of Cancer, vol.20, issue.3, pp.403-409, 1997.
DOI : 10.1002/(SICI)1097-0215(19971104)73:3<403::AID-IJC15>3.0.CO;2-D

B. M. Dunn and S. Hung, The two sides of enzyme???substrate specificity: lessons from the aspartic proteinases, Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, vol.1477, issue.1-2, pp.231-240, 2000.
DOI : 10.1016/S0167-4838(99)00275-7

O. Schilling and C. M. Overall, Proteome-derived, database-searchable peptide libraries for identifying protease cleavage sites, Nature Biotechnology, vol.5, issue.6, pp.685-694, 2008.
DOI : 10.1038/nbt1408

M. Lkhider, R. Castino, E. Bouguyon, C. Isidoro, and M. Ollivier-bousquet, Cathepsin D released by lactating rat mammary epithelial cells is involved in prolactin cleavage under physiological conditions, Journal of Cell Science, vol.117, issue.21, pp.5155-5164, 2004.
DOI : 10.1242/jcs.01396

D. Piwnica, I. Fernandez, N. Binart, P. Touraine, P. A. Kelly et al., A New Mechanism for Prolactin Processing into 16K PRL by Secreted Cathepsin D, Molecular Endocrinology, vol.20, issue.12, pp.3263-3278, 2006.
DOI : 10.1210/me.2006-0044

N. H. Yamada and . Huh, Truncation of annexin A1 is a regulatory lever for linking epidermal growth factor signaling with cytosolic phospholipase A2 in normal and malignant squamous epithelial cells, J Biol Chem, vol.282, pp.35679-35686, 2007.

B. Christensen, L. Schack, E. Klaning, and E. S. Sorensen, Osteopontin Is Cleaved at Multiple Sites Close to Its Integrin-binding Motifs in Milk and Is a Novel Substrate for Plasmin and Cathepsin D, Journal of Biological Chemistry, vol.285, issue.11, pp.7929-7937, 2010.
DOI : 10.1074/jbc.M109.075010

O. Schilling and C. M. Overall, Proteomic discovery of protease substrates, Current Opinion in Chemical Biology, vol.11, issue.1, pp.36-45, 2007.
DOI : 10.1016/j.cbpa.2006.11.037

C. M. Overall and C. P. Blobel, In search of partners: linking extracellular proteases to substrates, Nature Reviews Molecular Cell Biology, vol.6, issue.3, pp.245-257, 2007.
DOI : 10.1038/nrm2120

A. Doucet and C. M. Overall, Protease proteomics: Revealing protease in vivo functions using systems biology approaches, Molecular Aspects of Medicine, vol.29, issue.5, pp.339-358, 2008.
DOI : 10.1016/j.mam.2008.04.003

G. S. Butler, R. A. Dean, D. Smith, and C. M. Overall, Membrane Protease Degradomics: Proteomic Identification and Quantification of Cell Surface Protease Substrates, Methods Mol Biol, vol.528, pp.159-176, 2009.
DOI : 10.1007/978-1-60327-310-7_12

R. A. Dean and C. M. Overall, Proteomics Discovery of Metalloproteinase Substrates in the Cellular Context by iTRAQTM Labeling Reveals a Diverse MMP-2 Substrate Degradome, Molecular & Cellular Proteomics, vol.6, issue.4, pp.611-623, 2007.
DOI : 10.1074/mcp.M600341-MCP200

P. L. Faust, S. Kornfeld, and J. M. Chirgwin, Cloning and sequence analysis of cDNA for human cathepsin D., Proceedings of the National Academy of Sciences, vol.82, issue.15, pp.4910-4914, 1985.
DOI : 10.1073/pnas.82.15.4910