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Frye, Fabianne

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Frye

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Fabianne

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Frye, Fabianne

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Author's Publications: search.filters.isAuthorOfPublication.18402170-82a6-4080-a2f3-48ed283cf321

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    PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival
    (Public Library of Science, 2010) Iida, Naoko; Zou, Lihua; Yao, Jun; Lu, Yiling; Epstein, Charles B.; Natesan, Sridaran; Mills, Gordon B.; Irie, Hanna Yoko; Shrestha, Yashaswi; Selfors, Laura; Frye, Fabianne; Wang, Zhigang C.; Richardson, Andrea; Polyak, Kornelia; Hahn, William; Brugge, Joan
    Background: Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets for therapeutic intervention since this property is believed to be critical for survival of tumor cells displaced from their natural niches. Anchorage-independent survival is induced by growth factor receptor hyperactivation in many cell types. We aimed to identify molecules that critically regulate IGF-1-induced anchorage-independent survival. Methods and Results: We conducted a high-throughput siRNA screen and identified PTK6 as a critical component of IGF-1 receptor (IGF-1R)-induced anchorage-independent survival of mammary epithelial cells. PTK6 downregulation induces apoptosis of breast and ovarian cancer cells deprived of matrix attachment, whereas its overexpression enhances survival. Reverse-phase protein arrays and subsequent analyses revealed that PTK6 forms a complex with IGF-1R and the adaptor protein IRS-1, and modulates anchorage-independent survival by regulating IGF-1R expression and phosphorylation. PTK6 is highly expressed not only in the previously reported Her2\(^+\) breast cancer subtype, but also in high grade ER\(^+\), Luminal B tumors and high expression is associated with adverse outcomes. Conclusions: These findings highlight PTK6 as a critical regulator of anchorage-independent survival of breast and ovarian tumor cells via modulation of IGF-1 receptor signaling, thus supporting PTK6 as a potential therapeutic target for multiple tumor types. The combined genomic and proteomic approaches in this report provide an effective strategy for identifying oncogenes and their mechanism of action.