Ni‐induced TGF‐β signaling promotes VEGF‐a secretion via integrin β3 upregulation. Issue 12 (7th May 2019)

• Record Type: Journal Article
• Authors: Wu, Chih‐Hsien; Ko, Jiunn‐Liang; Pan, Hui‐Hsien; Chiu, Ling‐Yen; Kang, Yu‐Ting; Hsiao, Yu‐Ping
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 12(2019:Dec.)
• Page Start: 22093
• Page End: 22102
• Publication Date: 2019-05-07
• Subjects: integrin β3 -- lung cancer -- nickel -- TGF‐β -- VEGF‐a; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28772
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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 (NiCl2 ) on the progression of cancer during metastasis. The results of showed that NiCl2 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 NiCl2 ‐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 NiCl2 ‐treated cells. In conclusion, NiCl2 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. Abstract : Nickel compounds are associated with lung and skin cancer incidence increase and accumulation of nickel in the body contributes to carcinogenesis. NiCl2 induces the expression of ITGB3 through TGF‐β signaling activation, followed by increasing vascular endothelial growth factor‐a secretion, revealing a novel role for ITGB3 in nickel compound‐induced cancer metastasis and tumor angiogenesis