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• W2125244982 startingPage "e11729" @default.
• W2125244982 abstract "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." @default.
• W2125244982 created "2016-06-24" @default.
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• W2125244982 date "2010-07-23" @default.
• W2125244982 modified "2023-10-15" @default.
• W2125244982 title "PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival" @default.
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• W2125244982 doi "https://doi.org/10.1371/journal.pone.0011729" @default.
• W2125244982 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2909213" @default.
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• W2125244982 hasPublicationYear "2010" @default.
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