title: Aberrant expression of human ortholog of mammalian enabled (hMena) in human colorectal carcinomas: implications for its role in tumor progression.
abstract: The human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoprotein (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility. Increasing evidence suggests that hMena over-expression is involved in human breast cancers, whereas the significance of hMena expression in colorectal carcinomas remains to be elucidated. In this study, we assessed the relative mRNA level of hMena using real-time PCR, showing that there is a statistically significant increase of hMena transcripts in matched human colorectal carcinomas and adjacent non-neoplastic colorectal epithelium (n=6, P=0.046). We also performed immunohistochemical analysis of the expression of hMena protein in 50 cases of paraffin-embedded archival colorectal tissues, and found that an elevated hMena expression is correlated to the cases with advanced TNM stages of colorectal carcinomas (P<0.001). On further inspection of immunohistochemical features of each specimen, we observed intensified hMena staining in the invasive front of colorectal carcinomas, especially in tumor budding, a transition from glandular structure to single or small clusters of cells at the invasive front. We demonstrated that there was a significantly increased hMena staining in the tumor budding as compared with more morphologically-differentiated areas of colorectal carcinomas, indicating that hMena over-expression may have a role in the initial steps of tumor invasion from primary sites. We performed in vitro motility assays to show that transient hMena transfection markedly enhanced the chemotactic/chemokinetic activity of HeLaS3 cells (P<0.001). Taken together, these results suggest that hMena over-expression is implicated in the progression of colorectal carcinomas by positively affecting the migratory phenotype of cancer cells.
authors.affiliation: Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Toyoda
authors.forename: Hidetada
authors.initials: H
authors.lastname: Kawana
authors.forename: Kouji
authors.initials: K
authors.lastname: Azuhata
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yu
authors.forename: Aya
authors.initials: A
authors.lastname: Omata
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kishi
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harigaya
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D015153:Blotting, Western; D002465:Cell Movement; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C511939:Enah protein, human; D008840:Microfilament Proteins; D012333:RNA, Messenger