title: Urocortin attenuates TGFβ1-induced Snail1 and slug expressions: inhibitory role of Smad7 in Smad2/3 signaling in breast cancer cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, Jiangsu Provincial key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, Jiangsu Provincial key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Jiangsu Provincial key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Jiangsu Provincial key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chuanhua
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Jiangsu Provincial key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chunxuan
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Jiangsu Provincial key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, Jiangsu Provincial key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D054832:Urocortins / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011743:Pyrimidines; D011758:Pyrroles; C000604407:SNAI1 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051906:Smad7 Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C576814:UCN protein, human; D054832:Urocortins; C103016:antalarmin; C116607:antisauvagine 30
keywords: SLUG; SMAD2/3; SMAD7; SNAIL1; TGFβ1; UROCORTIN