The POPX2 phosphatase regulates cancer cell motility and invasiveness

Agatha Susila, Hei Chan, Andrew Xiong Wen Loh, Hui Qun Phang, Ee Tsin Wong, Vinay Tergaonkar, Cheng Gee Koh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Rho Gtpases play major roles in the regulation of actin cytoskeleton, cell movement and cell cycle. pAK, one of the effector kinases of these small Gtpases, has long been associated with different types of cancer. therefore, it is likely that deregulation of pAK activity or expression may contribute to the development of cancer. popX2, a pp2C serine/threonine phosphatase, is known to dephosphorylate PAK and downregulate its activity. We find that POPX2 is expressed in a wide variety of tumour cell lines, the levels being highest in the more invasive MDA-MB-231 and lowest in the non-invasive MCF7 breast cancer lines. We show that silencing of POPX2 reduces the amount of stress fibers and focal adhesions in both cells lines. Interestingly, POPX2 deficiency dramatically reduces cell motility and invasiveness in MDA-MB-231 cells, and cell motility in MCF7 cells. Conversely, overexpression of popX2 in MDA-MB-231 and MCF7 cells increased their motility. the silencing of popX2 also inhibits the expression of beta1 integrin implying that popX2 may modulate cell attachment to the extra-cellular matrix, as reflected in diminished initial colonization of POPX2 knockdown cells in nude mice. Based on these results, we propose a mechanism by which popX2 regulates the invasive behavior of the cells.

Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalCell Cycle
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 1 2010
Externally publishedYes

ASJC Scopus Subject Areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Keywords

  • Beta1 integrin
  • Cell adhesion
  • Cell motility
  • PAK kinase
  • Phosphatase
  • SRF transcription

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