C. Anderberg, S. I. Cunha, Z. Zhai, E. Cortez, E. Pardali et al., Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination, J. Exp. Med, vol.210, pp.563-579, 2013.

D. Banerjee, S. M. Barton, P. W. Grabham, A. L. Rumeld, S. Okochi et al., High-dose radiation increases notch1 in tumor vasculature, Int. J. Radiat. Oncol. Biol. Phys, vol.106, pp.857-866, 2020.

L. Bu, H. Baba, N. Yoshida, K. Miyake, T. Yasuda et al., Biological heterogeneity and versatility of cancer-associated fibroblasts in the tumor microenvironment, Oncogene, vol.38, pp.4887-4901, 2019.

X. Chen, J. Cai, X. Zhou, L. Chen, Y. Gong et al., Protective effect of spironolactone on endothelial-to-mesenchymal transition in HUVECs via notch pathway, Cell Physiol. Biochem, vol.36, pp.191-200, 2015.

J. G. Cho, A. Lee, W. Chang, M. S. Lee, K. et al., Endothelial to mesenchymal transition represents a key link in the interaction between inflammation and endothelial dysfunction, Front. Immunol, vol.9, p.294, 2018.

S. H. Choi, Z. Y. Hong, J. K. Nam, H. J. Lee, J. Jang et al., A Hypoxia-induced vascular endothelial-to-mesenchymal transition in development of radiation-induced pulmonary fibrosis, Clin. Cancer Res, vol.21, pp.3716-3726, 2015.

S. H. Choi, A. R. Kim, J. K. Nam, J. M. Kim, J. Y. Kim et al., Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6(+) cancer cell and macrophage polarization, Nat. Commun, vol.9, p.5108, 2017.

, Biophys. Acta Mol. Cell Res, vol.1864, pp.2283-2296

E. Dejana, K. K. Hirschi, and M. Simons, The molecular basis of endothelial cell plasticity, Nat. Commun, vol.8, p.14361, 2017.

F. Djouadi, F. Aubey, D. Schlemmer, J. P. Ruiter, R. J. Wanders et al., Bezafibrate increases very-long-chain acyl-CoA dehydrogenase protein and mRNA expression in deficient fibroblasts and is a potential therapy for fatty acid oxidation disorders, Hum. Mol. Genet, vol.14, pp.2695-2703, 2005.
URL : https://hal.archives-ouvertes.fr/inserm-02896287

M. Doerr, J. Morrison, L. Bergeron, B. L. Coomber, and A. Viloria-petit, Differential effect of hypoxia on early endothelial-mesenchymal transition response to transforming growth beta isoforms 1 and 2, Microvasc. Res, vol.108, pp.48-63, 2016.

G. Eelen, P. De-zeeuw, L. Treps, U. Harjes, B. W. Wong et al., Endothelial cell metabolism, Physiol. Rev, vol.98, pp.3-58, 2018.

C. S. Fan, L. L. Chen, T. A. Hsu, C. C. Chen, K. V. Chua et al., Endothelial-mesenchymal transition harnesses HSP90alpha-secreting M2-macrophages to exacerbate pancreatic ductal adenocarcinoma, J. Hematol. Oncol, vol.12, p.138, 2019.

C. S. Fan, W. S. Chen, L. L. Chen, C. C. Chen, Y. T. Hsu et al., Osteopontin-integrin engagement induces HIF-1alpha-TCF12-mediated endothelial-mesenchymal transition to exacerbate colorectal cancer, Oncotarget, vol.9, pp.4998-5015, 2018.

J. Folkman, Tumor angiogenesis: therapeutic implications, N. Engl. J. Med, vol.285, pp.1182-1186, 1971.

S. C. Formenti, R. E. Hawtin, N. Dixit, E. Evensen, P. Lee et al., Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients, J. Immunother. Cancer, vol.7, p.177, 2019.

M. Franco, P. Roswall, E. Cortez, D. Hanahan, and K. Pietras, Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression, Blood, vol.118, pp.2906-2917, 2011.

H. Gao, J. Zhang, T. Liu, and W. Shi, Rapamycin prevents endothelial cell migration by inhibiting the endothelial-to-mesenchymal transition and matrix metalloproteinase-2 and -9: an in vitro study, Mol. Vis, vol.17, pp.3406-3414, 2011.

V. C. Garside, A. C. Chang, A. Karsan, and P. A. Hoodless, Co-ordinating Notch, BMP, and TGF-beta signaling during heart valve development, Cell Mol. Life Sci, vol.70, pp.2899-2917, 2013.

A. Gasparics, L. Rosivall, I. A. Krizbai, and A. Sebe, When the endothelium scores an own goal: endothelial cells actively augment metastatic extravasation through endothelial-mesenchymal transition, Am. J. Physiol. Heart Circ. Physiol, vol.310, 2016.

P. Ghiabi, J. Jiang, J. Pasquier, M. Maleki, N. Abu-kaoud et al., Breast cancer cells promote a notch-dependent mesenchymal phenotype in endothelial cells participating to a pro-tumoral niche, J. Transl. Med, vol.13, p.27, 2015.

S. F. Glaser, A. W. Heumuller, L. Tombor, P. Hofmann, M. Muhly-reinholz et al., The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition, Proc. Natl. Acad. Sci. U.S.A, vol.117, pp.4180-4187, 2020.

G. T. Gonzalez-mateo, A. R. Aguirre, J. Loureiro, H. Abensur, P. Sandoval et al., Rapamycin protects from type-i peritoneal membrane failure inhibiting the angiogenesis, lymphangiogenesis, and Endo-MT, Biomed. Res. Int, p.989560, 2015.

J. Goveia, K. Rohlenova, F. Taverna, L. Treps, L. C. Conradi et al., An Integrated Gene expression landscape profiling approach to identify lung tumor endothelial cell heterogeneity and angiogenic candidates, Cancer Cell, vol.37, pp.21-36, 2020.

A. Gu, Y. Jie, Q. Yao, Y. Zhang, and E. Mingyan, Slug is associated with tumor metastasis and angiogenesis in ovarian cancer, Reprod. Sci, vol.24, pp.291-299, 2017.

I. Helfrich, I. Scheffrahn, S. Bartling, J. Weis, V. Von-felbert et al., Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma, J. Exp. Med, vol.207, pp.491-503, 2010.

M. Huang, T. Liu, P. Ma, R. A. Mitteer, and Z. Zhang, c-Met-mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma, J. Clin. Invest, vol.126, pp.1801-1814, 2016.

M. Huang, D. Zhang, J. Y. Wu, K. Xing, E. Yeo et al., Wntmediated endothelial transformation into mesenchymal stem cell-like cells induces chemoresistance in glioblastoma, Sci. Transl. Med, vol.12, p.532, 2020.

M. S. Hulshoff, X. Xu, G. Krenning, and E. M. Zeisberg, Epigenetic regulation of endothelial-to-mesenchymal, 2018.

, Arterioscler. Thromb. Vasc. Biol, vol.38, 1986.

S. P. Hung, M. H. Yang, K. F. Tseng, and O. K. Lee, Hypoxia-induced secretion of TGF-beta1 in mesenchymal stem cell promotes breast cancer cell progression, Cell Transplant, vol.22, pp.1869-1882, 2013.

A. Italiano, O. Mir, S. Mathoulin-pelissier, N. Penel, S. Piperno-neumann et al., Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial, Lancet Oncol, vol.21, pp.446-455, 2020.

J. Kim, MicroRNAs as critical regulators of the endothelial to mesenchymal transition in vascular biology, BMB Rep, vol.51, pp.65-72, 2018.

S. H. Kim, Y. Song, and H. R. Seo, GSK-3beta regulates the endothelialto-mesenchymal transition via reciprocal crosstalk between NSCLC cells and HUVECs in multicellular tumor spheroid models, J. Exp. Clin. Cancer Res, vol.38, p.46, 2019.

T. Kokudo, Y. Suzuki, Y. Yoshimatsu, T. Yamazaki, T. Watabe et al., Snail is required for TGFbeta-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells, J. Cell Sci, vol.121, pp.3317-3324, 2008.

R. J. Kovacs, G. Maldonado, A. Azaro, M. S. Fernandez, F. L. Romero et al., Cardiac safety of TGF-beta receptor i kinase inhibitor LY2157299 monohydrate in cancer patients in a first-in-human dose study, Cardiovasc. Toxicol, vol.15, pp.309-323, 2015.

I. A. Krizbai, A. Gasparics, P. Nagyoszi, C. Fazakas, J. Molnar et al., Endothelial-mesenchymal transition of brain endothelial cells: possible role during metastatic extravasation, PLoS One, vol.10, p.119655, 2015.

Y. Li, K. O. Lui, and B. Zhou, Reassessing endothelial-to-mesenchymal transition in cardiovascular diseases, Nat. Rev. Cardiol, vol.15, pp.445-456, 2018.

Y. Li, C. Zhong, D. Liu, W. Yu, W. Chen et al., Evidence for kaposi sarcoma originating from mesenchymal stem cell through KSHVinduced mesenchymal-to-endothelial transition, Cancer Res, vol.78, pp.230-245, 2018.

L. Liu, J. Chen, L. Sun, and Y. Xu, RhoJ promotes hypoxia induced endothelial-to-mesenchymal transition by activating WDR5 expression, J. Cell Biochem, vol.119, pp.3384-3393, 2018.

T. Liu, W. Ma, H. Xu, M. Huang, D. Zhang et al., PDGFmediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma, Nat. Commun, vol.9, p.3439, 2018.

N. Maishi, D. A. Annan, H. Kikuchi, Y. Hida, and K. Hida, Tumor endothelial heterogeneity in cancer progression, Cancers, vol.11, p.1511, 2019.

M. Maleszewska, R. A. Gjaltema, G. Krenning, and M. C. Harmsen, Enhancer of zeste homolog-2 (EZH2) methyltransferase regulates transgelin/smooth muscle-22alpha expression in endothelial cells in response to interleukin-1beta and transforming growth factor-beta2, Cell Signal, vol.27, pp.1589-1596, 2015.

S. Maman and I. P. Witz, A history of exploring cancer in context, Nat. Rev. Cancer, vol.18, pp.359-376, 2018.

T. Mammoto, M. Muyleart, G. G. Konduri, and A. Mammoto, Twist1 in hypoxia-induced pulmonary hypertension through transforming growth factor-beta-smad signaling, Am. J. Respir. Cell Mol. Biol, vol.58, pp.194-207, 2018.

N. I. Marin-ramos, N. Jhaveri, T. Z. Thein, R. A. Fayngor, T. C. Chen et al., NEO212, a conjugate of temozolomide and perillyl alcohol, blocks the endothelial-to-mesenchymal transition in tumor-associated brain endothelial cells in glioblastoma, Cancer Lett, vol.442, pp.170-180, 2019.

D. Medici, S. Potenta, and R. Kalluri, Transforming growth factor-beta2 promotes Snail-mediated endothelial-mesenchymal transition through convergence of Smad-dependent and Smad-independent signalling, Biochem. J, vol.437, pp.515-520, 2011.

H. Mihira, H. I. Suzuki, Y. Akatsu, Y. Yoshimatsu, T. Igarashi et al., TGF-beta-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A, J. Biochem, vol.151, pp.145-156, 2012.

E. Mintet, E. Rannou, V. Buard, G. West, O. Guipaud et al., identification of endothelial-to-mesenchymal transition as a potential participant in radiation Proctitis, Am. J. Pathol, vol.185, pp.2550-2562, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02572571

S. Murugavel, A. Bugyei-twum, P. N. Matkar, H. Al-mubarak, H. H. Chen et al., Valproic acid induces endothelial-to-mesenchymal transition-like phenotypic switching, Front. Pharmacol, vol.9, p.737, 2018.

N. Nagai, H. Ohguchi, R. Nakaki, Y. Matsumura, Y. Kanki et al., Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition, PLoS Genet, vol.14, p.1007826, 2018.

L. Nie, O. Lyros, R. Medda, N. Jovanovic, J. L. Schmidt et al., Endothelial-mesenchymal transition in normal human esophageal endothelial cells cocultured with esophageal adenocarcinoma cells: role of IL-1beta and TGF-beta2, Am. J. Physiol. Cell Physiol, vol.307, pp.859-877, 2014.

H. Nishi, T. Nakada, M. Hokamura, Y. Osakabe, O. Itokazu et al., Hypoxia-inducible factor-1 transactivates transforming growth factor-beta3 in trophoblast, Endocrinology, vol.145, pp.4113-4118, 2004.

, Epigenetics as a unifying principle in the aetiology of complex traits and diseases, Frontiers in Cell and Developmental Biology | www.frontiersin.org Petronis, A, vol.465, pp.721-727, 2010.

S. Piera-velazquez and S. A. Jimenez, Endothelial to mesenchymal transition: role in physiology and in the pathogenesis of human diseases, Physiol. Rev, vol.99, pp.1281-1324, 2018.

S. Potenta, E. Zeisberg, and R. Kalluri, The role of endothelial-tomesenchymal transition in cancer progression, Br. J. Cancer, vol.99, pp.1375-1379, 2008.

M. Potente, H. Gerhardt, and P. Carmeliet, Basic and therapeutic aspects of angiogenesis, Cell, vol.146, pp.873-887, 2011.

D. R. Principe, J. A. Doll, J. Bauer, B. Jung, H. G. Munshi et al., TGF-beta: duality of function between tumor prevention and carcinogenesis, J. Natl. Cancer Inst, vol.106, p.369, 2014.

D. F. Quail, J. , and J. A. , Microenvironmental regulation of tumor progression and metastasis, Nat. Med, vol.19, pp.1423-1437, 2013.

F. Rieder, S. P. Kessler, G. A. West, S. Bhilocha, C. De-la-motte et al., Inflammation-induced endothelial-to-mesenchymal transition: a novel mechanism of intestinal fibrosis, Am. J. Pathol, vol.179, pp.2660-2673, 2011.

K. Rohlenova, J. Goveia, M. Garcia-caballero, A. Subramanian, J. Kalucka et al., Single-Cell RNA sequencing maps endothelial metabolic plasticity in pathological angiogenesis, Cell Metab, vol.31, pp.862-877, 2020.

S. Schoors, U. Bruning, R. Missiaen, K. C. Queiroz, G. Borgers et al., Fatty acid carbon is essential for dNTP synthesis in endothelial cells, Nature, vol.520, pp.192-197, 2015.

T. Suzuki, E. J. Carrier, M. H. Talati, A. Rathinasabapathy, X. Chen et al., Isolation and characterization of endothelial-to-mesenchymal transition cells in pulmonary arterial hypertension, Am. J. Physiol. Lung Cell Mol. Physiol, vol.314, pp.118-126, 2018.

H. Tang, A. Babicheva, K. M. Mcdermott, Y. Gu, R. J. Ayon et al., Endothelial HIF-2alpha contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition, Am. J. Physiol. Lung Cell. Mol. Physiol, vol.314, pp.256-275, 2018.

J. N. Thupari, E. K. Kim, T. H. Moran, G. V. Ronnett, and F. P. Kuhajda, , 2004.

, Chronic C75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass, Am. J. Physiol. Endocrinol. Metab, vol.287, pp.97-104

A. Toullec, V. Buard, E. Rannou, G. Tarlet, O. Guipaud et al., , 2018.

, HIF-1alpha deletion in the endothelium, but not in the epithelium, protects from radiation-induced enteritis, Cell Mol. Gastroenterol. Hepatol, vol.5

T. Tsutsumi, T. Nagaoka, T. Yoshida, L. Wang, S. Kuriyama et al., Nintedanib ameliorates experimental pulmonary arterial hypertension via inhibition of endothelial mesenchymal transition and smooth muscle cell proliferation, PLoS One, vol.14, p.214697, 2019.

S. H. Wang, J. S. Chang, J. R. Hsiao, Y. C. Yen, S. S. Jiang et al., Tumour cell-derived WNT5B modulates in vitro lymphangiogenesis via induction of partial endothelial-mesenchymal transition of lymphatic endothelial cells, Oncogene, vol.36, pp.1503-1515, 2017.

M. E. Wawro, K. Chojnacka, K. Wieczorek-szukala, K. Sobierajska, and J. Niewiarowska, Invasive colon cancer cells induce transdifferentiation of endothelium to cancer-associated fibroblasts through microtubules enriched in tubulin-beta3, Int. J. Mol. Sci, vol.20, p.53, 2018.

K. M. Welch-reardon, N. Wu, and C. C. Hughes, A role for partial endothelial-mesenchymal transitions in angiogenesis?, Arterioscler. Thromb. Vasc. Biol, vol.35, pp.303-308, 2015.

Y. Xiang, Y. Zhang, Y. Tang, L. , and Q. , MALAT1 modulates tgf-beta1-induced endothelial-to-mesenchymal transition through downregulation of miR-145, Cell Physiol. Biochem, vol.42, pp.357-372, 2017.

L. Xiao and A. C. Dudley, Fine-tuning vascular fate during endothelialmesenchymal transition, J. Pathol, vol.241, pp.25-35, 2017.

L. Xiao, D. J. Kim, C. L. Davis, J. V. Mccann, J. M. Dunleavey et al., Tumor endothelial cells with distinct patterns of TGFbetadriven endothelial-to-mesenchymal transition, Cancer Res, vol.75, pp.1244-1254, 2015.

J. Xiong, H. Kawagishi, Y. Yan, J. Liu, Q. S. Wells et al., A metabolic basis for endothelial-to-mesenchymal transition, Mol. Cell, vol.69, pp.689-698, 2018.

X. Xu, X. Tan, B. Tampe, E. Sanchez, M. Zeisberg et al., Snail is a direct target of hypoxia-inducible factor 1alpha (HIF1alpha) in hypoxia-induced endothelial to mesenchymal transition of human coronary endothelial cells, J. Biol. Chem, vol.290, pp.16653-16664, 2015.

N. O. Yamada, K. Heishima, Y. Akao, and T. Senda, Extracellular vesicles containing microRNA-92a-3p facilitate partial endothelial-mesenchymal transition and angiogenesis in endothelial cells, Int. J. Mol. Sci, vol.20, p.406, 2019.

E. M. Zeisberg, S. Potenta, L. Xie, M. Zeisberg, and R. Kalluri, Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts, Cancer Res, vol.67, pp.10123-10128, 2007.

K. Zhu, Q. Pan, L. Q. Jia, Z. Dai, A. W. Ke et al., MiR-302c inhibits tumor growth of hepatocellular carcinoma by suppressing the endothelial-mesenchymal transition of endothelial cells, Sci. Rep, vol.4, p.5524, 2014.