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GPCR Signaling Mediates Tumor Metastasis via PI3K?.

ABSTRACT: Inappropriate activation of PI3K signaling has been implicated strongly in human cancer. Although studies on the role of PI3K signaling in breast tumorigenesis and progression have focused most intensively on PI3K?, a role for PI3K? has begun to emerge. The PI3K? isoform is unique among class IA PI3K enzymes in that it is activated by both receptor tyrosine kinases and G-protein-coupled receptors (GPCR). In previous work, we identified a mutation that specifically abolishes PI3K? binding to G?? (p110(526KK-DD)). Expression of this mutant in p110?-silenced breast cancer cells inhibits multiple steps of the metastatic cascade in vitro and in vivo and causes a cell autonomous defect in invadopodial matrix degradation. Our results identify a novel link between GPCRs and PI3K? in mediating metastasis, suggesting that disruption of this link might offer a novel therapeutic target to prevent the development of metastatic disease. Cancer Res; 76(10); 2944-53. ©2016 AACR.

SUBMITTER: Khalil BD

PROVIDER: S-EPMC4915222 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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GPCR Signaling Mediates Tumor Metastasis via PI3Kβ.

Khalil Bassem D BD Hsueh Christine C Cao Yanyan Y Abi Saab Widian F WF Wang Yarong Y Condeelis John S JS Bresnick Anne R AR Backer Jonathan M JM

Cancer research 20160324 10

Inappropriate activation of PI3K signaling has been implicated strongly in human cancer. Although studies on the role of PI3K signaling in breast tumorigenesis and progression have focused most intensively on PI3Kα, a role for PI3Kβ has begun to emerge. The PI3Kβ isoform is unique among class IA PI3K enzymes in that it is activated by both receptor tyrosine kinases and G-protein-coupled receptors (GPCR). In previous work, we identified a mutation that specifically abolishes PI3Kβ binding to Gβγ ...[more]

PMID: 27013201

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