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Metastasis Signaling Pathways

Abstract A82: The role of PI3-kinase signaling pathway in invadopodia formation

Hideki Yamaguchi, Nachi Yoshida and Ryuichi Sakai
Hideki Yamaguchi
National Cancer Center Research Institute, Tokyo, Japan.
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Nachi Yoshida
National Cancer Center Research Institute, Tokyo, Japan.
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Ryuichi Sakai
National Cancer Center Research Institute, Tokyo, Japan.
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DOI: 10.1158/1538-7445.TIM2013-A82 Published February 2013
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Abstract

Degradation of extracellular matrix that is present in the basement membrane and tumor stroma is essential for local invasion and formation of metastatic sites by malignant cancer cells. Invadopodia are extracellular matrix-degrading protrusions formed by invasive cancer cells that have been shown to function in cancer invasion and metastasis. Although many invadopodia components have been identified, signaling pathways that link extracellular stimuli to invadopodia formation remain poorly understood. The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate phosphoinositides at the D-3 position of the inositol headgroup. PI3Ks mediate the signal transduction of extracellular stimuli and regulate diverse cellular events. Uncontrolled activation of the PI3K signaling pathway leads to tumorigenesis and tumor malignancy. In this study, we investigated the role of PI3K signaling during invadopodia formation. We found 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 suppressed invadopodia formation induced by p110α mutants. These data suggest that PI3K signaling via p110α regulates invadopodia-mediated invasion of breast cancer cells.

Citation Format: Hideki Yamaguchi, Nachi Yoshida, Ryuichi Sakai. The role of PI3-kinase signaling pathway in invadopodia formation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A82.

  • ©2013 American Association for Cancer Research.
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Cancer Research: 73 (3 Supplement)
February 2013
Volume 73, Issue 3 Supplement
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Abstract A82: The role of PI3-kinase signaling pathway in invadopodia formation
Hideki Yamaguchi, Nachi Yoshida and Ryuichi Sakai
Cancer Res February 1 2013 (73) (3 Supplement) A82; DOI: 10.1158/1538-7445.TIM2013-A82

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Abstract A82: The role of PI3-kinase signaling pathway in invadopodia formation
Hideki Yamaguchi, Nachi Yoshida and Ryuichi Sakai
Cancer Res February 1 2013 (73) (3 Supplement) A82; DOI: 10.1158/1538-7445.TIM2013-A82
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Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

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