RalB regulates contractility-driven cancer dissemination upon TGFβ stimulation via the RhoGEF GEF-H1.
作者： Marco Biondini , Guillaume Duclos , Nathalie Meyer-Schaller , Pascal Silberzan , Jacques Camonis
DOI: 10.1038/SREP11759
关键词:
摘要: RalA and RalB proteins are key mediators of oncogenic Ras signaling in human oncogenesis. Herein we investigated the mechanistic contribution Ral to invasion lung cancer A549 cells after induction epithelial-mesenchymal transition (EMT) with TGFβ. We show that TGFβ-induced EMT promotes dissemination a 2/3D assay, independently proteolysis, by activating Rho/ROCK pathway which generates actomyosin-dependent contractility forces actively remodel extracellular matrix, as assessed Traction Force microscopy. RalB, but not RalA, is required for matrix deformation cell acting via RhoGEF GEF-H1, associates Exocyst complex, major effector. Indeed, uncoupling subunit Sec5 from GEF-H1 impairs RhoA activation, generation traction dissemination. These results provide novel molecular mechanism underlying control cross-talk Rho pathway.
nature.com
harvard.edu
sci-hub.se 参考文章(51)
Bettina Weigelin, Gert-Jan Bakker, Peter Friedl, Intravital third harmonic generation microscopy of collective melanoma cell invasion: Principles of interface guidance and microvesicle dynamics. Intravital. ,vol. 1, pp. 32- 43 ,(2012) , 10.4161/INTV.21223
Justin R. Tse, Adam J. Engler, Preparation of Hydrogel Substrates with Tunable Mechanical Properties Current Protocols in Cell Biology. ,vol. 47, ,(2010) , 10.1002/0471143030.CB1016S47
Hidenori Kasai, Jeremy T Allen, Roger M Mason, Takashi Kamimura, Zhi Zhang, TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT) Respiratory Research. ,vol. 6, pp. 56- 56 ,(2005) , 10.1186/1465-9921-6-56
Samy Lamouille, Jian Xu, Rik Derynck, Molecular mechanisms of epithelial–mesenchymal transition Nature Reviews Molecular Cell Biology. ,vol. 15, pp. 178- 196 ,(2014) , 10.1038/NRM3758
Victoria Sanz-Moreno, Gilles Gadea, Jessica Ahn, Hugh Paterson, Pierfrancesco Marra, Sophie Pinner, Erik Sahai, Christopher J Marshall, None, Rac Activation and Inactivation Control Plasticity of Tumor Cell Movement Cell. ,vol. 135, pp. 510- 523 ,(2008) , 10.1016/J.CELL.2008.09.043
Jane Cullis, David Meiri, Maria Jose Sandi, Nikolina Radulovich, Oliver A. Kent, Mauricio Medrano, Daphna Mokady, Josee Normand, Jose Larose, Richard Marcotte, Christopher B. Marshall, Mitsuhiko Ikura, Troy Ketela, Jason Moffat, Benjamin G. Neel, Anne-Claude Gingras, Ming-Sound Tsao, Robert Rottapel, The RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1. Cancer Cell. ,vol. 25, pp. 181- 195 ,(2014) , 10.1016/J.CCR.2014.01.025
Lisa M Coussens, Barbara Fingleton, Lynn M Matrisian, Matrix Metalloproteinase Inhibitors and Cancer--Trials and Tribulations Science. ,vol. 295, pp. 2387- 2392 ,(2002) , 10.1126/SCIENCE.1067100
Yunneng Tang, Guangwen Shu, Xinwang Yuan, Naihe Jing, Jianguo Song, FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers Cell Research. ,vol. 21, pp. 316- 326 ,(2011) , 10.1038/CR.2010.126
Brian O. Bodemann, Michael A. White, Ral GTPases and cancer: linchpin support of the tumorigenic platform Nature Reviews Cancer. ,vol. 8, pp. 133- 140 ,(2008) , 10.1038/NRC2296
Kai Kessenbrock, Vicki Plaks, Zena Werb, Matrix Metalloproteinases: Regulators of the Tumor Microenvironment Cell. ,vol. 141, pp. 52- 67 ,(2010) , 10.1016/J.CELL.2010.03.015