The interaction of p130Cas with PKN3 promotes malignant growth. Issue 2 (3rd December 2018)

• Record Type: Journal Article
• Authors: Gemperle, Jakub; Dibus, Michal; Koudelková, Lenka; Rosel, Daniel; Brábek, Jan
• Is Part Of: Molecular oncology. Volume 13:Issue 2(2019)
• Page Start: 264
• Page End: 289
• Publication Date: 2018-12-03
• Subjects: BCAR1 -- CAS -- p130Cas -- PKN3 -- SH3 -- Src; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12401
• Languages: English
• ISSNs: 1574-7891

Abstract

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 mechanism distinct from that previously characterized for p130Cas. Together, our results suggest that the PKN3–p130Cas complex represents an attractive therapeutic target in late‐stage malignancies. Abstract : Adaptor protein p130Cas controls actin cytoskeleton remodeling and regulates cancer cell progression induced by diverse oncogenes. Here, we characterize a novel direct interactor of p130Cas, pro‐malignant Ser/Thr kinase PKN3. We show that PKN3 phosphorylates p130Cas and colocalizes with p130Cas to pro‐invasive cell structures, and that PKN3‐p130Cas interaction is required for increased cell invasiveness and malignant/tumor growth, thus cooperating in cancer progression.