Intestinal adenomagenesis involves core molecular signatures of the epithelial-mesenchymal transition.
The epithelial-mesenchymal transition (EMT) occurs commonly during carcinoma invasion and metastasis, but not during early tumorigenesis. Microarray data demonstrated elevation of vimentin, a mesenchymal marker, in intestinal adenomas from Apc Min/+ (Min) mice. We have tested the involvement of EMT in early tumorigenesis in mammalian intestines by following EMT-associated markers. Elevated vimentin RNA expression and protein production were detected within neoplastic cells in murine intestinal adenomas. Similarly, vimentin protein was detected in both adenomas and invasive adenocarcinomas of the human colon, but not in the normal colonic epithelium or in hyperplastic polyps. Expression of E-cadherin varied inversely with vimentin. In addition, the expression of fibronectin was elevated while that of E-cadherin decreased. Canonical E-cadherin suppressors, such as Snail, were not elevated in the same tumor. Elevated vimentin expression in the adenoma was not correlated with persistent Ras signaling, but was strongly correlated with reduced proliferation indices, active Wnt signaling, and TGF-beta signaling, as demonstrated by its dependence on Smad3. We designate our observations of expression of only some of the canonical features of EMT as "truncated EMT". These unexpected observations are interpreted as reflecting the involvement of a core of the EMT system during the tissue remodeling of early tumorigenesis.
Chen
Xiaodi
X
McArdle Laboratory for Cancer Research, University of Wisconsin, 1400 University Avenue, Madison, WI 53706, USA.
Halberg
Richard B
RB
Burch
Ryan P
RP
Dove
William F
WF
D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D001397:Azoxymethane; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D004848:Epithelium / Q000473:pathology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D007417:Intestinal Polyps / Q000473:pathology; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D010641:Phenotype; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins; D005353:Fibronectins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014746:Vimentin; D051153:Wnt Proteins; D018631:ras Proteins; D001397:Azoxymethane