Open AccessPI (3,4)P 2 plays critical roles in the regulation of focal adhesion dynamics of MDA ‐ MB ‐231 breast cancer cells
Author(s) -
Fukumoto Miki,
Ijuin Takeshi,
Takenawa Tadaomi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13215
Subject(s) - gene knockdown , focal adhesion , pi , phosphatidylinositol , invadopodia , microbiology and biotechnology , phosphatase , pten , chemistry , cancer research , cancer cell , biology , pi3k/akt/mtor pathway , cancer , signal transduction , phosphorylation , apoptosis , biochemistry , genetics
Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4‐bisphosphate ( PI (3,4)P 2 ) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI (3,4)P 2 on focal adhesion dynamics in MDA ‐ MB ‐231 basal breast cancer cells. Knockdown of SHIP 2, a phosphatidylinositol 3,4,5‐trisphosphatase ( PIP 3 ) 5‐phosphatase that generates PI (3,4)P 2 , 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 PIP 3 and PI (3,4)P 2 , induced cell shrinkage and increased cell invasion. Interestingly, additional knockdown of SHIP 2 rescued these phenotypes. Overexpression of the TAPP 1 PH domain, which binds to PI (3,4)P 2 , and knockdown of Lpd, a downstream effector of PI (3,4)P 2 , resulted in similar phenotypes to those induced by SHIP 2 knockdown. Taken together, our results suggest that inhibition of PI (3,4)P 2 generation and/or downstream signaling could be useful for inhibiting breast cancer metastasis.