« Back
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
Poster Views: 1,547
View poster »

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.
2. The PyMOL Molecular Graphics System, version 1.3; Schrö dinger, LLC: New York.
3. Irwin, J. J. et al., J. Med. Chem. 2009, 52, 5712−5720.
4. Lorber, D. M.; Shoichet, B. K., Curr. Top. Med. Chem. 2005, 5, 739−749.
5. Song, M.S., Salmena, L., Pandolfi, P.P., Nat. Rev. Mol. Cell Biol. 2012, 13, 283-296.
Ortega-Molina, A., Serrano, M., Trends in Endocrinology & Metabolism, 2013, 24, 184-189.
6. Lee, C. U., et al., Angew.Chem.Int.Ed.Engl., 2015, 54, 13796-13800.
7. Lee, J. O., et al., Cell, 1999, 99, 323-334.
Report abuse »
Ask the author a question about this poster.
Ask a Question »

Creative Commons