Revealing the Role of Cancer Testes Antigens in HIF Signaling

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Charles Okechukwu1,3, Joshua Wooten2 , Kathleen Corcoran2, PhD., Rebecca Sinnott2, Patrick Taus2 , Kimberly Maxfield2,AngeliqueWhitehurst, PhD.2

1 Department of Pharmaceutical Sciences, North Carolina Central University, Durham, North Carolina. 2 Department of Pharmacology, University of North Carolina Chapel-Hill, North Carolina. 3 PARTNERS Program, Center for Science, Math and Technology Education, North Carolina Central University, Durham, NC

Abstract

The hypoxia –inducible factor-1 (HIF-1α), is a transcription factor that responds to changes in oxygen homeostasis1. Furthermore, the HIF pathway has been observed to contribute to tumor aggressiveness. The overexpression of HIF proteins has been observed to increase malignancy in tumor cells. Identifying the mechanisms that regulate HIF is essential to developing therapeutic strategies to inhibit its function. Here, we asked whether any members of the cancer-testes (CT)-antigen (CTA) family support HIF signaling. We combined a siRNA mediated loss of function approach with a luciferase reporter fused to a HIF Response Element (HRE), to determine consequences on HIF signaling following individual depletion of 120 CTAs. This screen revealed that a subset of CT-antigens played a role in Hif1α protein binding to HRE. It was then shown, by western blot, that depletion of this subset of CTAs, MAGEA3/6 and IGF2BP3, lead to decreased Hif1α protein. These findings suggest that CTAs may support stress signaling, particularly under hypoxic conditions, and further demonstrate that CTAs may be playing functional roles in supporting tumor cell survival.

Funding support: Charles Okechukwu was supported by the PARTNERS Research and Training Program in Health Disparities, funded through grant 5-U54-CA156733 from the National Cancer Institute.

Contact Information: Charles Okechukwu-(919)282-6135, okechuk@eagles.nccu.edu/Sponsor- Dr. Sandra L.White (919)530-7060, swhite@nccu.edu.

Last Update: 01 October 2013

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