Induction of Integrin Signaling by Steroid Sulfatase in Human Cervical Cancer Cells.
10.4062/biomolther.2016.155
- Author:
Dong Jin YE
1
;
Yeo Jung KWON
;
Sangyun SHIN
;
Hyoung Seok BAEK
;
Dong Won SHIN
;
Young Jin CHUN
Author Information
1. College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea. yjchun@cau.ac.kr
- Publication Type:Original Article
- Keywords:
Steroid sulfatase;
Dehydroepiandrosterone;
Integrin β1;
FAK;
MAPK/ERK pathway
- MeSH:
Androgens;
Breast;
Cell Proliferation;
Dehydroepiandrosterone;
Estrogens;
Fibronectins;
Focal Adhesion Protein-Tyrosine Kinases;
HeLa Cells;
Humans*;
Hydrolysis;
Phosphorylation;
Prostatic Neoplasms;
RNA, Messenger;
Steryl-Sulfatase*;
Sulfates;
Up-Regulation;
Uterine Cervical Neoplasms*
- From:Biomolecules & Therapeutics
2017;25(3):321-328
- CountryRepublic of Korea
- Language:English
-
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 β1 and fibronectin, a ligand of integrin α5β1. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin β1 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 β1 and activation of FAK.
