期刊
MOLECULAR CARCINOGENESIS
卷 56, 期 2, 页码 580-593出版社
WILEY
DOI: 10.1002/mc.22518
关键词
zinc; breast cancer cells; cancer-associated fibroblasts; EGFR; GPER; IGF-IR
资金
- Associazione Italiana per la Ricerca sul Cancro [16719/2015 14066/13]
- Programma Operativo Nazionale Ricerca e Competitivita [PON 01_01078]
- Ministero della Salute [67/GR-2010-2319511]
- International Cancer Research Fellowship iCARE
- European Union (Marie Curie Actions)
Zinc (Zn) is an essential trace mineral that contributes to the regulation of several cellular functions; however, it may be also implicated in the progression of breast cancer through different mechanisms. It has been largely reported that the classical estrogen receptor (ER), as well as the G protein estrogen receptor (GPER, previously known as GPR30) can exert a main role in the development of breast tumors. In the present study, we demonstrate that zinc chloride (ZnCl2) involves GPER in the activation of insulin-like growth factor receptor I (IGF-IR)/epidermal growth factor receptor (EGFR)-mediated signaling, which in turn triggers downstream pathways like ERK and AKT in breast cancer cells, and main components of the tumor microenvironment namely cancer-associated fibroblasts (CAFs). Further corroborating these findings, ZnCl2 stimulates a functional crosstalk of GPER with IGF-IR and EGFR toward the transcription of diverse GPER target genes. Then, we show that GPER contributes to the stimulatory effects induced by ZnCl2 on cell-cycle progression, proliferation, and migration of breast cancer cells as well as migration of CAFs. Together, our data provide novel insights into the molecular mechanisms through which zinc may exert stimulatory effects in breast cancer cells and CAFs toward tumor progression. (c) 2016 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据