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bioRxiv · 10.1101/334425

The interaction of p130Cas with PKN3 promotes malignant growth

Gemperle, J.·Dibus, M.·Koudelkova, L.·Unsal-Kacmaz, K.·Rosel, D.·Brabek, J.
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Abstract

Protein p130Cas constitutes an adaptor protein mainly involved in integrin signaling downstream of Src kinase. Owing to its modular structure, p130Cas acts as a general regulator of cancer cell growth and invasiveness induced by different oncogenes. However, other mechanisms of p130Cas signaling leading to malignant progression are poorly understood. Here, we show a novel interaction of p130Cas with Ser/Thr kinase PKN3, which is implicated in prostate and breast cancer growth downstream of phosphoinositide 3-kinase. This direct interaction is mediated by the p130Cas SH3 domain and the centrally located PKN3 polyproline sequence. PKN3 is the first identified Ser/Thr kinase to bind and phosphorylate p130Cas and to colocalize with p130Cas in cell structures that have a pro-invasive function. Moreover, the PKN3-p130Cas interaction is important for mouse embryonic fibroblast growth and invasiveness independent of Src transformation, indicating a distinct mechanism from that previously characterized for p130Cas. Together, our results suggest that the PKN3-p130Cas complex may represent an attractive therapeutic target in late-stage malignancies.\n\nSummaryGemperle et al. present the first report of an interaction between p130Cas with the serine/threonine kinase PKN3, implicated in prostate and breast cancer growth. They show that p130Cas colocalizes with PKN3 in cell structures that have a pro-invasive function and enhance our understanding of PKN3-mediated signaling and tumor growth.

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Gemperle, J., Dibus, M., Koudelkova, L., Unsal-Kacmaz, K., Rosel, D., Brabek, J.. 2018-05-30. The interaction of p130Cas with PKN3 promotes malignant growth. https://doi.org/10.1101/334425

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