The POPX2 phosphatase regulates cancer cell motility and invasiveness.
Rho GTP ases play major roles in the regulation of actin cytoskeleton, cell movement and cell cycle. PAK, one of the effector kinases of these small GTP ases, 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. POP X2, a PP 2C 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 POP X2 in MDA-MB-231 and MCF7 cells increased their motility. The silencing of POP X2 also inhibits the expression of beta1 integrin implying that POP X2 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 POP X2 regulates the invasive behavior of the cells.
Susila
Agatha
A
School of Biological Sciences, Nanyang Technological University, Singapore.
Chan
Hei
H
Loh
Andrew Xiong-Wen
AX
Phang
Hui-Qun
HQ
Wong
Ee Tsin
ET
Tergaonkar
Vinay
V
Koh
Cheng-Gee
CG
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016133:Polymerase Chain Reaction; D022502:Stress Fibers / Q000235:genetics / Q000378:metabolism
C459194:PPM1F protein, human; D010749:Phosphoprotein Phosphatases