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Role of nuclear pore complex in ovarian cancer chemoresistance | 559
Translational Medicine

Translational Medicine
Open Access

ISSN: 2161-1025

+44 1223 790975

Role of nuclear pore complex in ovarian cancer chemoresistance


International Conference on Translational Medicine

September 17-19, 2012 Holiday Inn San Antonio, Texas, USA

Tamara Kalir

Scientific Tracks Abstracts: Transl Med

Abstract :

Although ovarian carcinoma ranks fifth among cancer-related deaths in American women, it is the leading cause of death from gynecologic malignancy in the U.S. The treatment mainstay for ovarian cancer historically has been and remains surgical debulking, followed by chemotherapy. Preferred first-line agents are cisplatin and carboplatin. The emergence of cancer cell multi-drug resistance has spurred research efforts toward developing countermeasures. Among the many methods of drug resistance employed by cancer cells, are malfunctioning plasma membrane transporter proteins. We took a novel approach of bypassing the plasma membrane, and investigated nuclear membrane pore complexes (NPCs). The NPC is a several hundred multiprotein complex spanning the nuclear envelope, which is flexibly expandable and functions in the transport of water soluble substances, including RNA, ribosomes, proteins, carbohydrates, signaling molecules and lipids across the nuclear membrane, via an energy-linked transport cycle. A nucleus may contain hundreds to thousands of NPCs, and each may perform up to one thousand translocations per second, hence its importance in intracellular communication. We found that the induction of alteration in the NPC via knockdown of one protein constituent, NUP62 conferred cisplatin resistance upon cultured high-grade ovarian carcinoma (TOV112D) cells. Further, preliminary studies have shown that NUP62 is phosphorylated in the coiled-coil domain by the protein tyrosine kinase PYK2. Activation of PYK2 is associated with chemoresistance in some tumor types, and as the coiled-coil domain mediates interactions between NUP62 and the NPC, phosphorylation of this domain may functionally alter nuclear pore architecture in a manner mimicked by NUP62 knockdown.

Biography :

Tamara Kalir, M.D., Ph.D. is Associate Professor of Pathology at The Mount Sinai School of Medicine, where she serves as Director of the Division of Gynecologic Pathology, Director of the Fellowship in Gynecologic Pathology, and works with co-researchers Stave Kohtz, Ph.D., and Yayoi Kinoshita, D.D.S., on nuclear pores in ovarian cancer chemoresistance.

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