title: Achaete scute-like 2 suppresses CDX2 expression and inhibits intestinal neoplastic epithelial cell differentiation.
abstract: The role of Achaete scute-like 2 (Ascl2) in colorectal cancer (CRC) cell differentiation is unknown. LS174T, HT-29 and Caco-2 cells have high Ascl2 expression, while Lovo and SW480 cells have low Ascl2 expression. LS174T and HT-29 cells with Ascl2 knockdown were transfected with caudal type homeobox 2 (CDX2) promoter constructs and used for luciferase assays and chromatin immunoprecipitation (ChIP) assays. Ascl2 knockdown promoted differentiation of CRC cells into a goblet cell phenotype, as determined by increased expression of MUC2, TFF3, and CDX2. Ascl2 knockdown activated CDX2 expression through a transcriptional mechanism via direct binding of Ascl2 to the proximal E-box of the CDX2 promoter. Ascl2 over-expression in Lovo and SW480 cells inhibited a goblet cell phenotype, as determined by reduced CDX2 and MUC2 expression. Inverse correlations between Ascl2 and CDX2, and Ascl2 and MUC2 mRNA levels, as well as Ascl2 and CDX2 protein levels were observed in CRC cancerous samples. This study demonstrates CDX2 repression by Ascl2 and highlights a role for Ascl2 in CRC cell differentiation. These findings suggest that the Ascl2/CDX2 axis may serve as a potential therapeutic target in colorectal cancer.
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Yangyang
authors: Y
authors: Shang
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Qiong
authors: Q
authors: Pan
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Lei
authors: L
authors: Chen
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Jun
authors: J
authors: Ye
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Xiaoli
authors: X
authors: Zhong
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Xiaohuan
authors: X
authors: Li
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Linkuan
authors: L
authors: Meng
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Jin
authors: J
authors: Guo
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Yin
authors: Y
authors: Tian
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Yonghong
authors: Y
authors: He
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Wensheng
authors: W
authors: Chen
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Zhihong
authors: Z
authors: Peng
authors: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China.
authors: Rongquan
authors: R
authors: Wang
mesh_terms: D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D012333:RNA, Messenger; C065501:ASCL2 protein, human; C491270:CDX2 protein, human
keywords: Achaete scute-like 2; CDX2; colorectal carcinoma; differentiation; transcriptional regulation