Please use this identifier to cite or link to this item: https://doi.org/10.1126/sciadv.aaz1534
Title: BNIP-2 retards breast cancer cell migration by coupling microtubule-mediated GEF-H1 and RhoA activation
Authors: Pan, M. 
Chew, Ti Weng 
Wong, Darren Chen Pei 
Xiao, J.
Ong, H.T. 
Li Chin, J.F. 
Low, B.C. 
Issue Date: 2020
Publisher: American Association for the Advancement of Science
Citation: Pan, M., Chew, Ti Weng, Wong, Darren Chen Pei, Xiao, J., Ong, H.T., Li Chin, J.F., Low, B.C. (2020). BNIP-2 retards breast cancer cell migration by coupling microtubule-mediated GEF-H1 and RhoA activation. Science Advances 6 (31) : eaaz1534. ScholarBank@NUS Repository. https://doi.org/10.1126/sciadv.aaz1534
Rights: Attribution 4.0 International
Abstract: Microtubules display dynamic turnover during cell migration, leading to cell contractility and focal adhesion maturation regulated by Rho guanosine triphosphatase activity. This interplay between microtubules and actomyosin is mediated by guanine nucleotide exchange factor (GEF)朒1 released after microtubule depolymerization or microtubule disconnection from focal adhesions. However, how GEF-H1 activates Rho upon microtubule disassembly remains elusive. Here, we found that BNIP-2, a BCH domain朿ontaining protein that binds both RhoA and GEF-H1 and traffics with kinesin-1 on microtubules, is important for GEF-H1杁riven RhoA activation upon microtubule disassembly. Depletion of BNIP-2 in MDA-MB-231 breast cancer cells decreases RhoA activity and promotes cell migration. Upon nocodazole-induced microtubule disassembly, the interaction between BNIP-2 and GEF-H1 increases, while knockdown of BNIP-2 reduces RhoA activation and cell rounding via uncoupling RhoA-GEF-H1 interaction. Together, these findings revealed that BNIP-2 couples microtubules and focal adhesions via scaffolding GEF-H1 and RhoA, fine-tuning RhoA activity and cell migration. Copyright � 2020 The Authors, some rights reserved.
Source Title: Science Advances
URI: https://scholarbank.nus.edu.sg/handle/10635/197685
ISSN: 23752548
DOI: 10.1126/sciadv.aaz1534
Rights: Attribution 4.0 International
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