Premium
Urocortin Attenuates TGFβ1‐Induced Snail1 and Slug Expressions: Inhibitory Role of Smad7 in Smad2/3 Signaling in Breast Cancer Cells
Author(s) -
Jin Lai,
Zhu Chao,
Wang Xiaofei,
Li Chuanhua,
Cao Chunxuan,
Yuan Jie,
Li Shengnan
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25194
Subject(s) - urocortin , signal transduction , transforming growth factor , slug , cancer research , epithelial–mesenchymal transition , downregulation and upregulation , biology , twist transcription factor , transforming growth factor beta , medicine , endocrinology , microbiology and biotechnology , receptor , chemistry , cancer , metastasis , biochemistry , gene
Corticortropin‐releasing hormone (CRH) family are multifunctional endocrine‐factors that regulate proliferation, apoptosis, and migration of various types of cancer cells. Deregulation of the transforming growth factor β1(TGFβ1) signal transduction promotes aggressive metastatic properties in late‐stage breast cancers. We previously have demonstrated in breast cancer cell line that CRH suppressed TGFβ1‐induced Epithelial‐Mesenchymal Transition (EMT) via induction of E‐cadherin. Our present data in MCF‐7 and MDA‐MB‐231 cells showed that Urocortin (Ucn, a member of CRH family) inhibited TGFβ1 signaling by reducing Smad2/3 activation and subsequent nuclear translocation through increasing Smad7 expression, leading to downregulation of Snail1 and Slug, the two EMT promoters. We further found that Antalarmin (CRH receptor type 1, CRHR1 antagonist) and Antisauvagine‐30 (CRH receptor type2, CRHR2 antagonist) abrogated the effects of Ucn on TGFβ1 signaling, implying that both active CRHR1 and CRHR2 participate in Ucn‐repressed TGFβ1 signaling. Our findings, for the fist time, identify Ucn as a potential mediator that inhibits oncogenic signaling by TGFβ1 and suggest that activating CRHR1 and R2 may prove effective in diminishing breast cancer progression stimulated by TGFβ1. J. Cell. Biochem. 116: 2494–2503, 2015. © 2015 Wiley Periodicals, Inc.