Phosphoinositide 3-kinase signaling pathway mediated by p110alpha regulates invadopodia formation.
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Yamaguchi H, Yoshida S, Muroi E, Yoshida N, Kawamura M, Kouchi Z, Nakamura Y, Sakai R, Fukami K
Phosphoinositide 3-kinase signaling pathway mediated by p110alpha regulates invadopodia formation.
J Cell Biol. 2011 Jun 27;193(7):1275-88. doi: 10.1083/jcb.201009126.
- PubMed ID
- 21708979 [ View in PubMed]
- Abstract
Invadopodia are extracellular matrix-degrading protrusions formed by invasive cancer cells that are thought to function in cancer invasion. Although many invadopodia components have been identified, signaling pathways that link extracellular stimuli to invadopodia formation remain largely unknown. We investigate the role of phosphoinositide 3-kinase (PI3K) signaling during invadopodia formation. We find that in human breast cancer cells, both invadopodia formation and degradation of a gelatin matrix were blocked by treatment with PI3K inhibitors or sequestration of D-3 phosphoinositides. Functional analyses revealed that among the PI3K family proteins, the class I PI3K catalytic subunit p110alpha, a frequently mutated gene product in human cancers, was selectively involved in invadopodia formation. The expression of p110alpha with cancerous mutations promoted invadopodia-mediated invasive activity. Furthermore, knockdown or inhibition of PDK1 and Akt, downstream effectors of PI3K signaling, suppressed invadopodia formation induced by p110alpha mutants. These data suggest that PI3K signaling via p110alpha regulates invadopodia-mediated invasion of breast cancer cells.