RRC ID 50059
Author Fukumoto M, Ijuin T, Takenawa T.
Title PI(3,4)P2 plays critical roles in the regulation of focal adhesion dynamics of MDA-MB-231 breast cancer cells.
Journal Cancer Sci
Abstract Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2 ) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI(3,4)P2 on focal adhesion dynamics in MDA-MB-231 basal breast cancer cells. Knockdown of SHIP2, a phosphatidylinositol 3,4,5-trisphosphatase (PIP3 ) 5-phosphatase that generates PI(3,4)P2 , in MDA-MB-231 breast cancer cells, induced the development of focal adhesions and cell spreading, leading to the suppression of invasion. In contrast, knockdown of PTEN, a 3-phosphatase that de-phosphorylates PIP3 and PI(3,4)P2 , induced cell shrinkage and increased cell invasion. Interestingly, additional knockdown of SHIP2 rescued these phenotypes. Overexpression of the TAPP1 PH domain, which binds to PI(3,4)P2 , and knockdown of Lpd, a downstream effector of PI(3,4)P2 , resulted in similar phenotypes to those induced by SHIP2 knockdown. Taken together, our results suggest that inhibition of PI(3,4)P2 generation and/or downstream signaling could be useful for inhibiting breast cancer metastasis.
Volume 108(5)
Pages 941-951
Published 2017-5-1
DOI 10.1111/cas.13215
PMID 28247964
PMC PMC5448597
MeSH Breast Neoplasms / metabolism* Breast Neoplasms / pathology* Cell Adhesion / physiology* Cell Line, Tumor Female Focal Adhesions / physiology* Humans Neoplasm Invasiveness / pathology PTEN Phosphohydrolase / metabolism Phosphatidylinositols / metabolism* Phosphorylation / physiology Signal Transduction / physiology
IF 4.966
Times Cited 17
DNA material pEGFP-C1-SHIP2 (RDB15719).