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Transforming Growth Factor-Beta-Induced Protein (TGFBI)/(βig-H3): A Matrix Protein with Dual Functions in Ovarian Cancer
Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, Research Centre for Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, South Australia, 5000, Australia
Research Centre for Infectious Diseases, School of Molecular Biosciences, University of Adelaide, South Australia 5005, Australia
Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia
* Author to whom correspondence should be addressed.
Received: 30 June 2012; in revised form: 3 August 2012 / Accepted: 16 August 2012 / Published: 21 August 2012
Abstract: Transforming growth factor-beta-induced protein (TGFBI, also known as βig-H3 and keratoepithelin) is an extracellular matrix protein that plays a role in a wide range of physiological and pathological conditions including diabetes, corneal dystrophy and tumorigenesis. Many reports indicate that βig-H3 functions as a tumor suppressor. Loss of βig-H3 expression has been described in several cancers including ovarian cancer and promoter hypermethylation has been identified as an important mechanism for the silencing of the TGFBI gene. Our recent findings that βig-H3 is down-regulated in ovarian cancer and that high concentrations of βig-H3 can induce ovarian cancer cell death support a tumor suppressor role. However, there is also convincing data in the literature reporting a tumor-promoting role for βig-H3. We have shown βig-H3 to be abundantly expressed by peritoneal cells and increase the metastatic potential of ovarian cancer cells by promoting cell motility, invasion, and adhesion to peritoneal cells. Our findings suggest that βig-H3 has dual functions and can act both as a tumor suppressor or tumor promoter depending on the tumor microenvironment. This article reviews the current understanding of βig-H3 function in cancer cells with particular focus on ovarian cancer.
Keywords: ovarian cancer; extracellular matrix; TGFBI; tumor suppressor; invasion; adhesion; metastasis
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Ween, M.P.; Oehler, M.K.; Ricciardelli, C. Transforming Growth Factor-Beta-Induced Protein (TGFBI)/(βig-H3): A Matrix Protein with Dual Functions in Ovarian Cancer. Int. J. Mol. Sci. 2012, 13, 10461-10477.
Ween MP, Oehler MK, Ricciardelli C. Transforming Growth Factor-Beta-Induced Protein (TGFBI)/(βig-H3): A Matrix Protein with Dual Functions in Ovarian Cancer. International Journal of Molecular Sciences. 2012; 13(8):10461-10477.
Ween, Miranda P.; Oehler, Martin K.; Ricciardelli, Carmela. 2012. "Transforming Growth Factor-Beta-Induced Protein (TGFBI)/(βig-H3): A Matrix Protein with Dual Functions in Ovarian Cancer." Int. J. Mol. Sci. 13, no. 8: 10461-10477.