EPS8 facilitates cellular growth and motility of colon cancer cells by increasing the expression and activity of focal adhesion kinase

Ming Chei Maa, Jenq-Chang Lee, Yen Jen Chen, Yun Ju Chen, Yuch Ching Lee, Shan-Tair Wang, Ching Chung Huang, Nan-Haw Chow, Tzeng-Horng Leu

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

In an attempt to study the role of Eps8 in human carcinogenesis, we observe that ectopic overexpression of Eps8 in SW480 cells (low Eps8 expression) increases cell proliferation. By contrast, expressing eps8 small interference RNA in SW620 and WiDr cells (high Eps8 expression) reduces their proliferation rate. Interestingly, attenuation of Eps8 decreases Src Pi-Tyr-416, Shc Pi-Tyr-317, and serum-induced FAK Pi-Tyr-397 and Pi-Tyr-861. Remarkably, by virtue of mammalian target of rapamycin/STAT3 Pi-Ser-727, Eps8 modulates FAK expression required for cell proliferation. Within 62% of colorectal tumor specimens examined, >2-fold enhancement of Eps8 as compared with their normal counterparts is observed, especially for those from the advanced stage. In agreement with the modulation of FAK by Eps8, the concomitant expression of these two proteins in tumor specimens is observed. Notably, Eps8 attenuation also impedes the motility of SW620 and WiDr cells, which can be rescued by ectopically expressed FAK. This finding discloses the indispensability of Eps8 and FAK in cell locomotion. These results provide a novel mechanism for Eps8-mediated FAK expression and activation in colon cancer cells.

Original languageEnglish
Pages (from-to)19399-19409
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number27
DOIs
Publication statusPublished - 2007 Jul 6

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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