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Fyn: A Key Regulator of Metastasis in Prostate Cancer

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Technical Report,01 May 2011,14 May 2015

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Cedars-Sinai Medical Center Chicago United States

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In this fourth and final year of DoD funding we have been finalizing a peer-reviewed manuscript entitled SRC family kinase FYN promotes the neuroendocrine phenotype and visceral metastasis in advanced prostate cancer. This manuscript is under review at Oncotarget. In this manuscript, we show that the loss of FYN abrogates the invasion of PC3 cells in response to the MET receptor ligand HGF. We also demonstrate that FYN contributes to the metastatic potential of NEPC cells in two mouse models of visceral metastasis. After the first submission of this manuscript, the reviewers expressed strong interest in our findings but they voiced a concern regarding the lack of data from a second prostate cancer cell line. During this past year, we have incorporated data from other prostate cancer lines including ARCaPm and LNCaP cells and we continue to been couraged that FYN is an attractive therapeutic and diagnostic target in PC. Also, our current data provide further support for ongoing clinical trials of FYN and MET inhibitors in castration-resistant PCa patients. As for future research directions, we have begun to explore the role of FYN in PDL1 expression in metastatic prostate cancer and the manner in which this kinase might be involved in prostate CTC activation.

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