Biomol Ther.  2017 May;25(3):321-328. 10.4062/biomolther.2016.155.

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

• Ye DJ
• Kwon YJ
• Shin S
• Baek HS
• Shin DW
• Chun YJ

• KMID: 2378811
• DOI: http://doi.org/10.4062/biomolther.2016.155

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.

Keyword

Steroid sulfatase; Dehydroepiandrosterone; Integrin β1; FAK; MAPK/ERK pathway

MeSH Terms

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*
Androgens
Dehydroepiandrosterone
Estrogens
Fibronectins
Focal Adhesion Protein-Tyrosine Kinases
RNA, Messenger
Steryl-Sulfatase
Sulfates