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http://dx.doi.org/10.4062/biomolther.2016.155

Induction of Integrin Signaling by Steroid Sulfatase in Human Cervical Cancer Cells  

Ye, Dong-Jin (College of Pharmacy, Chung-Ang University)
Kwon, Yeo-Jung (College of Pharmacy, Chung-Ang University)
Shin, Sangyun (College of Pharmacy, Chung-Ang University)
Baek, Hyoung-Seok (College of Pharmacy, Chung-Ang University)
Shin, Dong-Won (College of Pharmacy, Chung-Ang University)
Chun, Young-Jin (College of Pharmacy, Chung-Ang University)
Publication Information
Biomolecules & Therapeutics / v.25, no.3, 2017 , pp. 321-328 More about this Journal
Abstract
Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin ${\beta}1$ and fibronectin, a ligand of integrin ${\alpha}5{\beta}1$. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin ${\beta}1$ and fibronectin. Further, STS expression and DHEA treatment enhanced phosphorylation of focal adhesion kinase (FAK) at the Tyr 925 residue. Moreover, increased phosphorylation of ERK at Thr 202 and Tyr 204 residues by STS indicates that STS activates the MAPK/ERK pathway. In conclusion, these results suggest that STS expression and DHEA treatment may enhance MAPK/ERK signaling through up-regulation of integrin ${\beta}1$ and activation of FAK.
Keywords
Steroid sulfatase; Dehydroepiandrosterone; Integrin ${\beta}1$; FAK; MAPK/ERK pathway;
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