A role for Hath1, a bHLH transcription factor, in colon adenocarcinoma.
A significant reduction or loss of goblet cells is often observed in clinical samples of colon adenocarcinomas, which is the predominant form of colon carcinoma. Mice lacking Math1, a bHLH transcription factor downstream of the Notch signaling pathway, demonstrates that Math1 is necessary for cell fate determination of the intestinal secretory cells, including goblet cells. Examination of Hath1, the human orthologue of Math1, expression in multiple colon tumor samples and colon cancer cell lines reveals a dramatic decrease in Hath1 expression in colon tumor samples and colon cancer cell lines. Hath1 expression in the HT29 colon cancer cell line can significantly inhibit its proliferation and anchorage-independent growth both in vitro and in vivo. At the molecular level, Hath1 may regulate the expression of MUC2, a mucin secreted by goblet cells, and Hath1 may also be a novel factor normally repressed as a consequence of activation of the Wnt signaling pathway, which has been clearly implicated in colon tumorigenesis.
Leow
Ching Ching
CC
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080, USA. ching2@gene.com
Polakis
Paul
P
Gao
Wei-Qiang
WQ
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D055262:Mucin-2; D009077:Mucins / Q000378:metabolism; D015398:Signal Transduction
D051792:Basic Helix-Loop-Helix Proteins; D055262:Mucin-2; D009077:Mucins; C500942:ATOH1 protein, human; C500943:Atoh1 protein, mouse; C524625:MUC2 protein, human; C524626:Muc2 protein, mouse