Functions and Molecular Mechanisms of Stress-Induced Phosphoprotein-1 That Is Elevated in Ovarian Cancer

  • Wang, Tzu-Hao (PI)
  • Chao, Angel (CoPI)
  • Wang, Hsin-Shih (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Ovarian cancer is the leading cause of gynecological cancer death. The high case-fatality rate is mainly attributed to the fact that most ovarian cancers are undiagnosed until advanced stages, III or IV, where the cancer has spread beyond the pelvis. More tumor markers for early detection of ovarian cancer are thus warranted. Through a systematic proteomics search for biomarkers of ovarian cancer, we have identified stress-induced phosphoprotein-1 (STIP1) as a potential biomarker for ovarian cancer. Because of the presence of STIP1 in various types of cancers, we hypothesize that STIP1 may have anti-apoptotic and/or pro-growth nature. Based on our discovery that STIP1 is secreted from tumors, we hypothesize that STIP1 may be a means by which the cancer gains survival advantages by stimulating itself (autocrine) and remodeling its environment (paracrine). Since there are nuclear localization signal (NLS) and several phosphorylating sites in STIP1 protein, we speculate that a panel of kinases and phosphatases may regulate translocation of STIP1, which in turns exerts diverse functions. In this three-year project, we attempt to achieve four Specific Aims: (1) to delineate the changes in serum STIP1 levels during menstruation cycle and to test whether polymorphisms of STIP1 are associated with ovarian cancer, (2) to identify the functions of upregulated intracellular STIP1 in ovarian cancer cells, (3) to study how STIP1 is secreted from ovarian cancer cells, and (4) to elucidate how secreted STIP1 exerts action in an autocrine or paracrine fashion. After we have completed this three-year study, we will fill the current knowledge gaps about the role of STIP1 in tumor biology. Our further understanding of STIP1 may provide the foundation for future development of novel therapeutic strategies for human ovarian cancer by targeting STIP1.

Project IDs

Project ID:PC10101-2042
External Project ID:NSC100-2314-B182-016-MY3
StatusFinished
Effective start/end date01/08/1231/07/13

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