title: CRH suppressed TGFβ1-induced Epithelial-Mesenchymal Transition via induction of E-cadherin in breast cancer cells.
abstract: Since its discovery in biopsies from breast cancer patients, the effect of corticotropin-releasing hormone (CRH) on carcinoma progression is still unclear. Transforming growth factorβ1 (TGFβ1) promotes Epithelial-Mesenchymal Transition (EMT) and induces Snail1 and Twist1 expressions. Loss of epithelial cadherin (E-cadherin) mainly repressed by Snail1 and Twist1, has been considered as hallmark of Epithelial-Mesenchymal Transition (EMT). Two breast cancer cell lines, MCF-7 and MDA-MB-231 were used to investigate the effect of CRH on TGFβ1-induced EMT by transwell chamber. And HEK293 cells were transiently transfected with CRHR1 or CRHR2 to explore the definite effects of CRH receptor. We reported that CRH inhibited migration of human breast cancer cells through downregulation of Snail1 and Twist1, and subsequent upregulation of E-cadherin. CRH inhibited TGFβ1-mediated migration of MCF-7 via both CRHR1 and CRHR2 while this inhibition in MDA-MB-231 was mainly via CRHR2. Ectopic re-expression of CRHR1 or CRHR2 respectively in HEK293 cells increased E-cadherin expression after CRH stimulation. Furthermore, CRH repressed expression of mesenchymal marker, N-cadherin and induced expression of Occludin, inhibiting EMT in MCF-7 & MDA-MB-231. Our results suggest that CRH may function as a tumor suppressor, at least partly by regulating TGFβ1-mediated EMT. These results may contribute to uncovering the effect of CRH in breast tumorigenesis and progression.
authors.affiliation: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Internal Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chuanhua
authors.initials: C
authors.lastname: Li
authors.affiliation: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China. Electronic address: lishengnan656@hotmail.com.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D015820:Cadherins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D051879:Twist-Related Protein 1; C116607:antisauvagine 30; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: CRH; E-cadherin; Epithelial–Mesenchymal Transition; Migration; TGFβ1