, Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging, Histochem. Cell Biol, vol.130, pp.1105-1118, 2008.
, A tense situation: forcing tumour progression, Nat. Rev. Cancer, vol.9, pp.108-122, 2009.
, Force sensing by mechanical extension of the Src family kinase substrate p130Cas, Cell, vol.127, pp.1015-1026, 2006.
, Mechano-tranduction: a growing role for contractibility, Nature Rev. Mol. Cell Biol, vol.10, pp.34-43, 2009.
, Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics, Nature, vol.466, pp.263-266, 2010.
, A mechanosensitive transcriptional mechanism that controls angiogenesis, Nature, vol.457, pp.1103-1108, 2009.
, Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine, Proc. Natl Acad. Sci. USA, vol.106, pp.6309-6314, 2009.
, Mechanical control of cell flow in multicellular spheroids, Phys. Rev. Lett, vol.110, p.138103, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01138971
, Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors, Proc. Natl Acad. Sci. USA, vol.109, pp.15101-15108, 2012.
, Mechanical factors activate b-catenin-dependent oncogene expression in APC mouse colon, HFSP J, vol.2, pp.286-294, 2008.
, Wnt/b-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway, Mol. Cell. Biol, vol.22, pp.1172-1183, 2002.
, Activation of canonical WNT/b-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition, Cancer Lett, vol.325, pp.42-53, 2012.
, b-catenin tyrosine 654 phosphorylation increases Wnt signalling and intestinal tumorigenesis, Gut, vol.60, pp.1204-1212, 2011.
, Wnt/b-catenin signaling in development and disease, Cell, vol.127, pp.469-480, 2006.
, A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors, Proc. Natl Acad. Sci. USA, vol.91, pp.8969-8973, 1994.
, Preparation of aqueous magnetic liquids in alkaline and acidic media, IEEE Trans. Magn, vol.17, pp.1247-1248, 1981.
, Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation, Proc. Natl Acad. Sci. USA, vol.75, pp.4194-4198, 1978.
, Ultra magnetic liposomes for MR imaging, targeting, and hyperthermia, Langmuir, vol.28, pp.11834-11842, 2012.
, Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging, J. Am. Chem. Soc, vol.127, pp.10676-10685, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00162333
, Magnetic targeting of rhodamine-labeled superparamagnetic liposomes to solid tumors: in vivo tracking by fibered confocal fluorescence microscopy, Mol. Imaging, vol.6, pp.140-146, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00162290
, Sterically stabilized superparamagnetic liposomes for MR imaging and cancer therapy: pharmacokinetics and biodistribution, Int. J. Pharm, vol.344, pp.118-127, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00212124
, The effect of magnetic targeting on the uptake of magnetic-fluid-loaded liposomes by human prostatic adenocarcinoma cells, Biomaterials, vol.29, pp.4137-4145, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00327614
, Anti-estrogen-loaded superparamagnetic liposomes for intracellular magnetic targeting and treatment of breast cancer tumors, Adv. Funct. Mater, vol.21, pp.83-92, 2011.
, The specificities of protein kinase inhibitors: an update, Biochem. J, vol.371, pp.199-204, 2003.
, SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling, Mol. Cell. Biol, vol.20, pp.9018-9027, 2000.
, An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases, J. Clin. Endocrinol. Metab, vol.91, pp.4070-4076, 2006.
, Vandetanib for the treatment of thyroid cancer, Clin. Pharmacol. Ther, vol.91, pp.71-80, 2012.
, Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase, Mol. Cell. Endocrinol, vol.377, pp.1-6, 2013.
, Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer, J. Clin. Endocrinol. Metab, vol.98, pp.811-819, 2013.
, Sol-gel transition in agar-gelatin mixtures studied with transient elastography, IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol.53, pp.716-723, 2006.
, Shear wave elastography of tumor growth in a human breast cancer model with pathological correlation, Eur. Radiol, vol.23, pp.2079-2086, 2013.
, Supersonic shear imaging: A new technique for soft tissue elasticity mapping, IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol.51, pp.396-409, 2004.
, Shear wave elasticity imaging: A new ultrasonic technology of medical diagnostics, Ultrasound Med. Biol, vol.24, pp.1419-1435, 1998.
, A comparison of diets of blacks and whites in three areas of the United States, Nutr. Cancer, vol.20, pp.153-165, 1993.
, Extended Data Figure 6 | Mechanical activation of Ret in both Apc 1/1638N
, Inhibition of pTyr1062-Ret, pTyr654-b-catenin and Myc mechanical induction by the two additional inhibitors of Ret, vandetanib and ponatinib. Top, Tyr1062 phosphorylation of Ret under uni-axial compression (54.16 6 15% positive crypts of 236, n 5 7 mice), initiating at 1-min compression, compared to initiation of the b-catenin oncogenic pathway by phosphorylation of b-catenin on Tyr654 under uni-axial compression (69.82 6 8.7% positive crypts of 119, measured in n 5 2 mice) compared to control (13.97 6 2.7% positive crypts of 121, measured in n 5 2 mice) is inhibited in the presence of vandetanib (5.89 6 4.2% positive crypts of 102 total crypts observed, measured in n 5 2 mice) and ponatinib (9.13 6 3.3% positive crypts of 120 total crypts observed, measured in n 5 2 mice). Bottom, mechanical induction of Myc under uni-axial compression (50.5 6 0.2% positive crypts of 146, measured in n 5 2 mice) compared to control (11 6 0.2% positive crypts of 118, Screening of the mechanical activation of the Src family kinases known to phosphorylate b-catenin Tyr654 and to be mechanosensitive in cell culture. Ret activation by Ret Tyr1062 phosphorylation under uni-axial compression (see Extended Data Fig. 4d legend for statistics
, Apc 1/1638N 1 UML 1 magnet: 14.15 6 2.5% of pTyr1062-Ret-positive crypts out of 499 total crypts (measured in n 5 2 mice). c, Mechanical activation of pTyr1062-Ret kinase in non-UML-loaded local domains, after UML injection and magnet implantation. A strong phosphorylation of Ret Tyr1062 (green) was observed not only in the domains where UML were accumulated (not shown) but also in UML-absent domains (negative signal for fluorescent rhodamine, left) in Apc 1/1638N colons (measured in n 5 4 mice for each condition). d, No mechanical activation of pTyr1062-Ret kinase after UML injection in the absence of magnet in Apc-deficient colons, UML 1 magnet: measured in n 5 3 mice, 469 crypts), of pY654-b-catenin apically
, Increased phosphorylation of GSK-3b Ser9 was observed in the magnetized tissue at 2 weeks (33.8 6 0.4% of 307 crypts), compared to the non-magnetized control (12.7 6 5.15% of 560 crypts) and to the UML-injected colon sample without magnet (7.24 6 2% of 138 crypts) (measured in n 5 2 mice for each condition), Mechanical inactivation of GSK-3b through Ser9 phosphorylation and mechanical activation of the upstream Akt through Ser473 phosphorylation in magnetized Apc-deficient colon explants
, GSK-3b: control, 12.5 6 5.2% positive crypts out of 320 (measured in n 5 2 mice); compressed, 43.26 6 11% positive crypts out of 784 (measured in n 5 2 mice); compressed 1 sunitinib, 19.7 6 12% positive crypts out of 216 (measured in n 5 2 mice); compressed 1 vandetanib, 14.4 6 0.1% positive crypts out of 114 (measured in n 5 2 mice); compressed 1 ponatinib, 15.45 6 5.6% positive crypts out of 230 (measured in n 5 2 mice for each condition), Ret-dependent mechanical inactivation of GSK-3b and activation of the upstream Akt after ex vivo global compression of Apc-deficient colon explants
, Note that at 1 month after tamoxifen injection, GFP expression is often diffuse and found in the nuclei and cytoplasm. Immunofluorescence staining and ImageJ co-localization analysis revealed an enrichment of nuclear b-catenin (white and purple spots represent a positive co-localization between b-catenin (red) and DAPI (blue)) by a factor of 5.8 in Notch/Apc colon samples 1 month after tamoxifen injection (11.64 6 2.5 a.u., measured in n 5 2 mice), compared to the control (1.99 6 0.8 a.u., measured in n 5 2 mice). Bottom, phosphorylation of b-catenin Y654 in Notch-negative crypts in tamoxifen-injected crypts (measured in n 5 4 mice, 68 crypts, yellow arrows) compared to nontamoxifen-injected control conditions (measured in n 5 4 mice, 198 crypts). Cytoplasmic enrichment and nuclear translocation of b-catenin in Notchnegative crypts, RESEARCH LETTER Extended Data Figure 8 | Notch/Apc colon shows an activation of the Ret/bcatenin/Myc mechanotransductive signalling pathway one month after tumour growth initiation. a, Top, Ret Y1062 phosphorylation
, RESEARCH LETTER G2015 Macmillan Publishers Limited. All rights reserved
, Ret phosphorylation was activated in 12.7 6 2.3% of Notch-negative crypts (22 pTyr1062-Ret-positive crypts of a total of 177 GFP-negative crypts) completely surrounded by Notch-negative crypts (GFP-negative), measured in n 5 4 mice. b, No phosphorylation of Ret Tyr1062 in Notch-overexpressing cells in early tumorous Notch/Apc colon explants. 34.9 6 8.8% of GFP-positive crypts (yellow arrows) showed no expression of pTyr1062-Ret (39 crypts out of a total of 113 crypts, measured in n 5 4 mice). c, Strain deformation of Notch/Apc 4 days after tamoxifen injection, Extended Data Figure 9 | Ret activation is non-cell autonomously induced by the mechanical strains developed by tumour pressure in Notch/Apc mice. a, Early mechanical activation of pTyr1062-Ret kinase in crypts totally surrounded by a Notch-negative domain in tumorous Notch/Apc colon explants