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Activation of PTEN lipid phosphatase function in lung cancer
Poster Title: Activation of PTEN lipid phosphatase function in lung cancer
Submitted on 08 Feb 2017
Author(s): Emily Palumbo, Peng Teng, Prerna Malaney, Michael Kemp, Zhi Tian, Diane Allen-Gipson, Yu Chen, Jianfeng Cai, Vrushank Dave
Affiliations: Depts of Pathology and Cell Biology, Morsani College of Medicine; Depts. of Chemistry, College of Arts and Sciences; Depts. of Molecular Medicine, Morsani College of Medicine; USF College of Pharmacy; H. Lee Moffitt Cancer Center, USF, Tampa, FL 33612
This poster was presented at USF Health Research Day 2017
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Poster Information
Abstract: The low frequency of mutations in tumor suppressor PTEN undermines its role in lung cancer. Instead, PTEN expression/function is often reduced in lung tumors via several non-genomic mechanisms, resulting in hyper-activation of the oncogenic PI3K/AKT pathway. Kinase inhibitor (KI) therapy remains challenging due to off-target effects and generation of alternative signaling cascades following treatment. Direct activation of PTEN phosphatase activity represents a novel alternative therapeutic paradigm to attenuate PI3K/AKT signaling. Herein, we identify and characterize peptidomimetics that enhance PTEN lipid phosphatase activity and attenuate PI3K/AKT pathway signaling. Further, select compounds reduced proliferation, migration and induced cell cycle arrest in lung cancer cells, thereby acting as anticancer agents. We have also elucidated optimal PTEN-peptidomimetic interactions in silico. In summary, we have discovered novel small molecule compounds that directly induce PTEN function and antagonize PI3K/AKT pathway activity in lung cancer cells.Summary: Loss of PTEN activity in cancer induces oncogenic PI3K/AKT/S6K kinase cascade signaling. Therapy with kinase inhibitors cause off-target effects and chemo-resistance, warranting the need for alternative therapy. Herein, we have identified novel peptidomimetics that enhance PTEN activity, attenuate PI3K/AKT pathway signaling and inhibit the oncogenic potential of lung cancer cells. PTEN activation represents a novel alternative therapeutic paradigm to mitigate PI3K/AKT/S6K signaling in cancers.References: 1. Kozakov, D., et al., Nat. Protoc. 2015, 10, 733−755.
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