PAK1 regulates RUFY3-mediated gastric cancer cell migration and invasion

Cell Death & Disease
G WangF Li

Abstract

Actin protrusion at the cell periphery is central to the formation of invadopodia during tumor cell migration and invasion. Although RUFY3 (RUN and FYVE domain containing 3)/SINGAR1 (single axon-related1)/RIPX (Rap2 interacting protein X) has an important role in neuronal development, its pathophysiologic role and relevance to cancer are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which RUFY3 involves in gastric cancer cell migration and invasion. Here, our data show that overexpression of RUFY3 leads to the formation of F-actin-enriched protrusive structures at the cell periphery and induces gastric cancer cell migration. Furthermore, P21-activated kinase-1 (PAK1) interacts with RUFY3, and promotes RUFY3 expression and RUFY3-induced gastric cancer cell migration; inhibition of PAK1 attenuates RUFY3-induced SGC-7901 cell migration and invasion. Importantly, we found that the inhibitory effect of cell migration and invasion is significantly enhanced by knockdown of both PAK1 and RUFY3 compared with knockdown of RUFY3 alone or PAK1 alone. Strikingly, we found significant upregulation of RUFY3 in gastric cancer samples with invasive carcinoma at pathologic TNM III and TNM IV stages...Continue Reading

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Citations

Mar 30, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xing-Hua XiaoLi-Xia Xiong
Oct 26, 2018·Bioscience Reports·Haixia ZhangXianzheng Wu
Mar 19, 2020·Journal of Biomolecular Structure & Dynamics·Shivangi Agarwal, Sushil K Kashaw
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Jun 22, 2021·Frontiers in Genetics·Haifeng XuTero Aittokallio

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Methods Mentioned

BETA
GTPase
two-hybrid
confocal microscopy
transfection
pull-down
immunoprecipitation
co-IP
transfections
PCR
in vitro transcription

Software Mentioned

Volocity

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