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Ni‐induced TGF‐β signaling promotes VEGF‐a secretion via integrin β3 upregulation
Author(s) -
Wu ChihHsien,
Ko JiunnLiang,
Pan HuiHsien,
Chiu LingYen,
Kang YuTing,
Hsiao YuPing
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28772
Subject(s) - downregulation and upregulation , angiogenesis , metastasis , cancer research , integrin , transforming growth factor , gene silencing , carcinogenesis , biology , mmp2 , endoglin , signal transduction , cancer , receptor , chemistry , microbiology and biotechnology , medicine , biochemistry , gene , stem cell , cd34
Nickel compounds are associated with lung and skin cancer incidence increase and accumulation of nickel in the body contributes to carcinogenesis. Upregulation of certain integrins in the primary tumor is associated with cancer metastasis and poor prognosis. However, the molecular mechanisms of nickel‐induced cancer metastasis are still unclear. The purpose of the present study was to investigate the effects of nickel chloride (NiCl 2 ) on the progression of cancer during metastasis. The results of showed that NiCl 2 induces the expression of integrin β3 mRNA and protein in a dose‐ and time‐dependent manner. Inhibition of integrin αvβ3 activation by ITGB3 ligand mimetics and GR144053, as well as downregulation of ITGB3 by lentiviral shRNA gene silencing, diminished NiCl 2 ‐induced secretion of vascular endothelial growth factor‐a (VEGF‐a). Furthermore, pretreatment with type I TGF‐β receptor inhibitor, SB525334, suppressed the expression of ITGB3 at cell surface and secretion of VEGF‐a in NiCl 2 ‐treated cells. In conclusion, NiCl 2 induces the expression of ITGB3 through TGF‐β signaling activation, followed by increasing VEGF‐a secretion, revealing a novel role for ITGB3 in nickel compound‐induced cancer metastasis and tumor angiogenesis.