Phosphoinositide 3-kinase signaling pathway mediated by p110α regulates invadopodia formation
0301 basic medicine
Breast Neoplasms
3. Good health
Class Ia Phosphatidylinositol 3-Kinase
Phosphatidylinositol 3-Kinases
03 medical and health sciences
Cell Line, Tumor
Humans
Female
Neoplasm Invasiveness
Proto-Oncogene Proteins c-akt
Research Articles
Phosphoinositide-3 Kinase Inhibitors
Signal Transduction
DOI:
10.1083/jcb.201009126
Publication Date:
2011-06-28T03:11:55Z
AUTHORS (9)
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 p110α, a frequently mutated gene product in human cancers, was selectively involved in invadopodia formation. The expression of p110α 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 p110α mutants. These data suggest that PI3K signaling via p110α regulates invadopodia-mediated invasion of breast cancer cells.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (67)
CITATIONS (112)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....