Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype
Final rept. 15 May 2011-14 May 2014
ALABAMA UNIV IN BIRMINGHAM
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The overarching goal of this research is to define the role of a cancer-associated glycosyltransferase, ST6Gal-I, in regulating the ovarian tumor cell phenotype. Results obtained as a consequence of DoD pilot funding have established that ST6Gal-I is overexpressed in the great majority of ovarian serous adenocarcinomas and associated metastases. ST6Gal-I adds an 2-6 linked sialic acid to selected membrane receptors including the 1 integrin, as well as the Fas and TNFR1 death receptors. In this final report, we show that ST6Gal-I-mediated receptor sialylation protects ovarian cancer cells against cell death within ascites fluid, suggesting that ST6Gal-I fosters cell survival during tumor cell transit through the peritoneal cavity. Additionally, ST6Gal-I appears to contribute to metastatic targeting of omentum and resistance to cisplatin chemotherapy. These collective findings provide new molecular insight into the important function of the glycosylation machinery in regulating tumor cell behavior. An aberrant profile of cell surface glycans was one of the earliest-identified hallmarks of a tumor cell, however tumor glycobiology has lagged behind most other areas of cancer cell biology. A seminal advance of this study is the determination that a distinct glycosyltransferase, acting on a specific subset of cell surface receptors, plays a critical role in the resistance of ovarian cancer cells to multiple death-inducing stimuli.
- Medicine and Medical Research