Abstract A47: Akt mediates prostate cancer cell migration and invasion via affinity modulation of integrin αvβ3

Abstract

Abstract Purpose: Prostate cancer cells often metastasize to the bones. The ability of prostate cancer cells to attach to several matrix proteins, migrate with a sense of direction in response to stimuli, invade to the adjacent tissue and enter the micro-circulation etc. are pre-requisites for them to metastasize to distant tissues. During this sojourn, prostate cancer cells keep transforming itself from one type to another by constantly changing the expression profile of its surface receptors and secreted factors, which in turn, helps them to respond to the cues from the micro-environment and mediate tumor progression. The current study is focused on the role of Akt kinase in the affinity modulation of integrin αvβ3 leading to prostate tumor invasion and metastasis. Methods: We used a number of tumor cell functional assay methods, molecular biology and biochemistry tools, immunocytochemistry, electric cell impedance sensing technology etc. to establish a correlation between Akt activity and inside-out activation (affinity modulation) of integrin αvβ3 leading to prostate cancer cell invasion and metastasis. Results: Our previous studies have shown that Akt is necessary for the affinity modulation of integrins in many normal cell types. Our results also implicated that Akt is necessary for prostate cancer cell functions such as proliferation, survival, invasion and migration. Current results revealed the involvement of Akt-mediated activation of integrin αvβ3 in human prostate cancer cells in vitro. We showed that Akt and integrin αvβ3 cooperation is required not only for tumor growth but also for invasion and further micro-metastasis to the blood vessels and eventually metastasis to the bone. Conclusion: Our study indicated a causal relationship between Akt activity, expression of integrin αvβ3 (that are not at all expressed by normal prostatic epithelial cells) and its inside-out activation (affinity modulation). We also conclude that Akt-mediated activation of integrin αvβ3 is necessary to initiate the switch in prostate cancer cells to invade and metastasis to distant tissues such as bone. Our study projects Akt and integrin αvβ3 as potential therapeutic targets for prostate cancer therapy. Citation Format: Anna Goc, Junxiu Liu, Tatiana Byzova, Somanath Shenoy. Akt mediates prostate cancer cell migration and invasion via affinity modulation of integrin αvβ3 [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A47.