TY - JOUR
T1 - RacGAP1-driven focal adhesion formation promotes melanoma transendothelial migration through mediating adherens junction disassembly
AU - Zhang, Pu
AU - Bai, Huiyuan
AU - Fu, Changliang
AU - Chen, Feng
AU - Zeng, Panying
AU - Wu, Chengxiang
AU - Ye, Qichao
AU - Dong, Cheng
AU - Song, Yang
AU - Song, Erqun
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2015/3/27
Y1 - 2015/3/27
N2 - Melanoma cell migration across vascular endothelial cells is an essential step of tumor metastasis. Here, we provide evidence that RacGAP1, a cytokinesis-related Rho GTPase-activating protein, contributed to this process. Depletion of RacGAP1 with RacGAP1-targeting siRNA or overexpression of RacGAP1 mutant (T249A) attenuated melanoma cell transendothelial migration and concomitant changes of adherens junctions. In addition, RacGAP1 promoted the activations of RhoA, FAK, paxillin and triggered focal adhesion formation and cytoskeletal rearrangement. By overexpressing FAK-related non-kinase (FRNK) in endothelium, we showed that RacGAP1 mediated endothelial barrier function loss and melanoma transmigration in a focal adhesion-dependent manner. These results suggest that endothelial RacGAP1 may play critical roles in pathogenic processes of cancer by regulating endothelial permeability.
AB - Melanoma cell migration across vascular endothelial cells is an essential step of tumor metastasis. Here, we provide evidence that RacGAP1, a cytokinesis-related Rho GTPase-activating protein, contributed to this process. Depletion of RacGAP1 with RacGAP1-targeting siRNA or overexpression of RacGAP1 mutant (T249A) attenuated melanoma cell transendothelial migration and concomitant changes of adherens junctions. In addition, RacGAP1 promoted the activations of RhoA, FAK, paxillin and triggered focal adhesion formation and cytoskeletal rearrangement. By overexpressing FAK-related non-kinase (FRNK) in endothelium, we showed that RacGAP1 mediated endothelial barrier function loss and melanoma transmigration in a focal adhesion-dependent manner. These results suggest that endothelial RacGAP1 may play critical roles in pathogenic processes of cancer by regulating endothelial permeability.
UR - http://www.scopus.com/inward/record.url?scp=84930082978&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930082978&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2014.11.088
DO - 10.1016/j.bbrc.2014.11.088
M3 - Article
C2 - 25475728
AN - SCOPUS:84930082978
SN - 0006-291X
VL - 459
SP - 1
EP - 9
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
