, oncotarget USA), and Cal51 from DSMZ

E. The, MCF-10A cell line was a generous gift of, Dr Kevin Struhl (Harvard Medical School

, The ER-Src MCF-10A cells contain an integrated fusion of the v-Src oncoprotein and the ligandbinding domain of estrogen receptor and are induced to rapidly transform when grown with 1 ?M as previously described [13]. YM155, Necrostatin-1 and BAY11-7085 were purchased from Selleck Chemicals (Houston, USA) and the pan-caspase inhibitor Q-VD-OPh from R&DSystems Chloroquine, 3-Methyl-Adenin (3-MA), Bafilomycin A1 were purchased from Sigma-Aldrich (Saint- Quentin Yvelines, France) AS602868 was a generous gift of Merck-Serono International SA [14]. Antibodies against Survivin was purchased from R&DSystems, All cell lines were cultured following supplier's recommendations antibodies against LC3 antibodies against HSP90, p53 and cleaved (i.e. activated) caspase3 from Becton Dickinson antibody against BAX from Dako), and antibody against p62 from Santa Cruz, pp.15-53

, REFERENCES

D. Altieri, Survivin, cancer networks and pathway-directed drug discovery, Nature Reviews Cancer, vol.65, issue.1, pp.61-70, 2008.
DOI : 10.1038/ni1413

A. Rauch, D. Hennig, C. Schäfer, M. Wirth, C. Marx et al., Survivin and YM155: How faithful is the liaison?, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, vol.1845, issue.2, pp.202-220, 2014.
DOI : 10.1016/j.bbcan.2014.01.003

T. Nakahara, A. Kita, K. Yamanaka, M. Mori, N. Amino et al., YM155, a Novel Small-Molecule Survivin Suppressant, Induces Regression of Established Human Hormone-Refractory Prostate Tumor Xenografts, Cancer Research, vol.67, issue.17, pp.8014-8021, 2007.
DOI : 10.1158/0008-5472.CAN-07-1343

A. Trocoli and M. Djavaheri-mergny, The complex interplay between autophagy and NF-?B signaling pathways in cancer cells, Am J Cancer Res, vol.1, pp.629-649, 2011.

N. Perkins, The diverse and complex roles of NF-??B subunits in cancer, Nature Reviews Cancer, vol.39, issue.2, pp.121-132, 2012.
DOI : 10.1093/nar/gkq929

G. Kroemer, G. Mariño, and B. Levine, Autophagy and the Integrated Stress Response, Molecular Cell, vol.40, issue.2, pp.280-293, 2010.
DOI : 10.1016/j.molcel.2010.09.023

F. Janku, D. Mcconkey, D. Hong, and R. Kurzrock, Autophagy as a target for anticancer therapy, Nature Reviews Clinical Oncology, vol.4, issue.9, pp.528-539, 2011.
DOI : 10.4161/auto.5338

E. White, Deconvoluting the context-dependent role for autophagy in cancer, Nature Reviews Cancer, vol.108, issue.6, pp.401-410, 2012.
DOI : 10.1073/pnas.1107969108

V. Baud and K. M. , Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls, Nat Rev Drug Discov, vol.1, pp.33-40, 2009.
URL : https://hal.archives-ouvertes.fr/inserm-00352349

K. Sarosiek, N. Chonghaile, T. Letai, and A. , Mitochondria: gatekeepers of response to chemotherapy, Trends in Cell Biology, vol.23, issue.12, pp.612-619, 2013.
DOI : 10.1016/j.tcb.2013.08.003

P. Juin, O. Geneste, F. Gautier, S. Depil, and M. Campone, Decoding and unlocking the BCL-2 dependency of cancer cells, Nature Reviews Cancer, vol.83, issue.7, pp.455-465, 2013.
DOI : 10.1016/j.bcp.2011.10.008

P. Czabotar, G. Lessene, A. Strasser, and J. Adams, Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy, Nature Reviews Molecular Cell Biology, vol.5, issue.1, pp.49-63, 2014.
DOI : 10.1038/sj.cdd.4402178

D. Iliopoulos, H. Hirsch, and K. Struhl, An Epigenetic Switch Involving NF-??B, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation, Cell, vol.139, issue.4, pp.693-706, 2009.
DOI : 10.1016/j.cell.2009.10.014

M. Romagnoli, G. Desplanques, S. Maïga, S. Legouill, M. Dreano et al., Canonical Nuclear Factor ??B Pathway Inhibition Blocks Myeloma Cell Growth and Induces Apoptosis in Strong Synergy with TRAIL, Clinical Cancer Research, vol.13, issue.20, pp.6010-6018, 2007.
DOI : 10.1158/1078-0432.CCR-07-0140

C. Séveno, D. Loussouarn, S. Bréchet, M. Campone, and P. Juin, ??-Secretase inhibition promotes cell death, Noxa upregulation, and sensitization to BH3 mimetic ABT-737 in human breast cancer cells, Breast Cancer Research, vol.435, issue.Suppl 1, p.96, 2012.
DOI : 10.1038/nature03659

T. Glaros, L. Stockwin, M. Mullendore, B. Smith, B. Morrison et al., The ???survivin suppressants??? NSC 80467 and YM155 induce a DNA damage response, Cancer Chemotherapy and Pharmacology, vol.282, issue.50, pp.207-212, 2012.
DOI : 10.1074/jbc.M706912200

M. Sun, W. Lou, J. Chun, D. Cho, N. Nadiminty et al., Sanguinarine Suppresses Prostate Tumor Growth and Inhibits Survivin Expression, Genes & Cancer, vol.1, issue.3, pp.283-292, 2010.
DOI : 10.1177/1947601910368849

URL : http://journals.sagepub.com/doi/pdf/10.1177/1947601910368849

G. Giaccone, P. Zatloukal, J. Roubec, K. Floor, J. Musil et al., Multicenter Phase II Trial of YM155, a Small-Molecule Suppressor of Survivin, in Patients With Advanced, Refractory, Non???Small-Cell Lung Cancer, Journal of Clinical Oncology, vol.27, issue.27, pp.4481-4476, 2009.
DOI : 10.1200/JCO.2008.21.1862

K. Lewis, W. Samlowski, J. Ward, J. Catlett, L. Cranmer et al., A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma, Investigational New Drugs, vol.26, issue.4, pp.161-166, 2011.
DOI : 10.1007/s10637-009-9333-6

V. Wagner, D. Hose, A. Seckinger, L. Weiz, T. Meißner et al., Preclinical efficacy of sepantronium bromide (YM155) in multiple myeloma is conferred by down regulation of Mcl-1, Oncotarget, vol.5, issue.21, pp.10237-10250, 2014.
DOI : 10.18632/oncotarget.2529

A. Faversani, V. Vaira, G. Moro, D. Tosi, A. Lopergolo et al., Survivin family proteins as novel molecular determinants of doxorubicin resistance in organotypic human breast tumors, Breast Cancer Research, vol.24, issue.3, p.55, 2014.
DOI : 10.1093/annonc/mdt249

URL : https://breast-cancer-research.biomedcentral.com/track/pdf/10.1186/bcr3666?site=breast-cancer-research.biomedcentral.com

K. Yamanaka, M. Nakata, N. Kaneko, H. Fushiki, A. Kita et al., YM155, a selective survivin suppressant, inhibits tumor spread and prolongs survival in a spontaneous metastatic model of human triple negative breast cancer, International Journal of Oncology, vol.39, pp.569-575, 2011.
DOI : 10.3892/ijo.2011.1077

D. Wood, A. Thomas, L. Devi, Y. Berman, R. Beavis et al., Bax cleavage is mediated by calpain during drug-induced apoptosis, Oncogene, vol.17, issue.9, pp.1069-1078, 1998.
DOI : 10.1038/sj.onc.1202034

URL : http://www.nature.com/onc/journal/v17/n9/pdf/1202034a.pdf

S. Storr, N. Carragher, M. Frame, T. Parr, and S. Martin, The calpain system and cancer, Nature Reviews Cancer, vol.4, issue.5, pp.364-374, 2011.
DOI : 10.1371/journal.pone.0008436

Q. Wang, Z. Chen, X. Diao, and S. Huang, Induction of autophagy-dependent apoptosis by the survivin suppressant YM155 in prostate cancer cells, Cancer Letters, vol.302, issue.1, pp.29-36, 2011.
DOI : 10.1016/j.canlet.2010.12.007

S. Cheng, Y. Chang, C. Liu, J. Lee, H. Chan et al., YM155 down-regulates Survivin and XIAP, modulates autophagy, and induces autophagydependent DNA damage in breast cancer cells, Br J Pharmacol, 2014.
DOI : 10.1111/bph.12935

URL : http://onlinelibrary.wiley.com/doi/10.1111/bph.12935/pdf

R. González-polo, P. Boya, A. Pauleau, A. Jalil, N. Larochette et al., The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death, Journal of Cell Science, vol.118, issue.14, pp.3091-3102, 2005.
DOI : 10.1242/jcs.02447

P. Boya and G. Kroemer, Lysosomal membrane permeabilization in cell death, Oncogene, vol.283, issue.50, pp.6434-351, 2008.
DOI : 10.1002/dvdy.21076

G. Winter, B. Radic, C. Mayor-ruiz, V. Blomen, C. Trefzer et al., Superti-Furga G. The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity, Nat Chem Biol, 2014.

T. Nakahara, A. Kita, K. Yamanaka, M. Mori, N. Amino et al., Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models, Cancer Science, vol.27, issue.3, pp.614-621, 2011.
DOI : 10.1200/JCO.2008.21.1862

Z. Wu, Y. Shi, R. Tibbetts, and S. Miyamoto, Molecular Linkage Between the Kinase ATM and NF-??B Signaling in Response to Genotoxic Stimuli, Science, vol.311, issue.5764, pp.1141-1146, 2006.
DOI : 10.1126/science.1121513

Z. Wu and S. Miyamoto, Induction of a pro-apoptotic ATM???NF-??B pathway and its repression by ATR in response to replication stress, The EMBO Journal, vol.408, issue.14, pp.1963-1973, 2008.
DOI : 10.4161/cc.6.4.3886

E. Strozyk, B. Pöppelmann, T. Schwarz, and D. Kulms, Differential effects of NF-??B on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome, Oncogene, vol.25, issue.47, pp.6239-6251, 2006.
DOI : 10.1038/sj.onc.1209655

T. Nakahara, K. Yamanaka, S. Hatakeyama, A. Kita, M. Takeuchi et al., YM155, a novel survivin suppressant, enhances taxane-induced apoptosis and tumor regression in a human Calu 6 lung cancer xenograft model, Anti-Cancer Drugs, vol.22, issue.5, pp.454-462, 2011.
DOI : 10.1097/CAD.0b013e328344ac68

K. Yamanaka, T. Nakahara, T. Yamauchi, A. Kita, M. Takeuchi et al., Antitumor Activity of YM155, a Selective Small-Molecule Survivin Suppressant, Alone and in Combination with Docetaxel in Human Malignant Melanoma Models, Clinical Cancer Research, vol.17, issue.16, pp.5423-5431, 2011.
DOI : 10.1158/1078-0432.CCR-10-3410

H. Tang, H. Shao, C. Yu, and J. Hou, Mcl-1 downregulation by YM155 contributes to its synergistic anti-tumor activities with ABT-263, Biochemical Pharmacology, vol.82, issue.9, pp.1066-1072, 2011.
DOI : 10.1016/j.bcp.2011.07.064

E. Jane, D. Premkumar, J. Didomenico, B. Hu, S. Cheng et al., YM-155 Potentiates the Effect of ABT-737 in Malignant Human Glioma Cells via Survivin and Mcl-1 Downregulation in an EGFR-Dependent Context, Molecular Cancer Therapeutics, vol.12, issue.3, pp.326-338, 2013.
DOI : 10.1158/1535-7163.MCT-12-0901