Transforming growth Factor-Beta-Induced Protein (TGFBI)/(βig-H3): a matrix protein with dual functions in ovarian cancer

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-...

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Bibliographic Details
Published in:International Journal of Molecular Sciences 2012-08, Vol.13 (8), p.10461-10477
Main Authors: Ween, Miranda P, Oehler, Martin K, Ricciardelli, Carmela
Format: Article
Language:English
Subjects:
adhesion
Cell Adhesion
Cell Movement
Cell Transformation, Neoplastic
DNA Methylation
extracellular matrix
Extracellular Matrix - metabolism
Extracellular Matrix Proteins - metabolism
Female
Humans
invasion
metastasis
ovarian cancer
Ovarian Neoplasms - metabolism
Review
TGFBI
Transforming Growth Factor beta - metabolism
tumor suppressor
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms130810461