Research ArticleCancer

Network Analysis of the Focal Adhesion to Invadopodia Transition Identifies a PI3K-PKCα Invasive Signaling Axis

Science Signaling  11 Sep 2012:
Vol. 5, Issue 241, pp. ra66
DOI: 10.1126/scisignal.2002964

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Becoming Invasive

Invasive and metastatic cancer cells form cellular protrusions called invadopodia that can degrade the extracellular matrix. Hoshino et al. integrated data from head and neck carcinomas with network analysis of invadopodia and focal adhesions, cellular structures that contain many of the same components as invadopodia but have decreased ability to degrade the extracellular matrix. They identified phosphatidylinositol 3-kinase (PI3K) and protein kinase C α (PKCα) as key determinants in the formation of invadopodia. The formation of invadopodia was enhanced by PKCα in cells with wild-type PI3K but was inhibited by PKCα in cells with enhanced PI3K activity (due to expression of components of the PI3K pathway with cancer-associated mutations). These results suggested that PKCα participated in a negative feedback loop that limited the activity of PI3K and thus cellular invasiveness, which the authors confirmed. The combination of high PI3K activity with low PKCα activity correlated with increased number of invadopodia in cell lines derived from head and neck carcinoma, breast cancer, or melanoma. This PI3K-high and PKCα-low signaling state may be useful as a biomarker for cancer aggressiveness.