Abstract

Abstract Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates. STS has a pivotal role in regulating the level of estrogen and androgen responsible for growth of hormone-dependent tumors, such as breast or prostate cancer. However, the molecular function for tumor growth of STS is still not clear. To elucidate possible role of STS on cancer cell proliferation, we investigated whether STS is able to regulate integrin signaling pathway. In this study, we observed that overexpression of STS in HeLa cells induces the expression of integrin β1 and fibronectin, a ligand of integrin α5β1 at protein and mRNA levels. Dehydroepiandrosterone (DHEA), one of the main metabolite of STS, also induces mRNA and protein level of integrin β1 and fibronectin. We found that STS expression and DHEA enhance phosphorylation of focal adhesion kinase (FAK) at tyrosine 925 residue. Moreover, phosphorylation of ERK at threonine 202 and tyrosine 204 residues was also induced, indicating that STS may activate Ras/Raf/MEK signaling pathway. In conclusion, these results suggest that STS expression and DHEA may enhance Ras/Raf/MEK signaling through upregulation of integrin β1 and activation of FAK. Citation Format: Dong-Jin Ye, Yeo-Jung Kwon, Sangyun Shin, Mihye Hong, Hyoungseok Baek, Seung-Ki Ahn, Dongwon Shin, Young-Jin Chun. Expression of steroid sulfatase induces the integrin signaling pathway in HeLa cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-A11.

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