Acetylcholinesterase supports anchorage independence in colon cancer.
Various roles have been attributed to Acetylcholinesterase (AChE) in cancer. Evidence exists for a pro-apoptotic function, consistent with a protective role of AChE. Because other reports suggested that upregulated AChE in some tumors may control cell adhesion, we tested the effects of AChE on anchorage independence (an essential component of metastasis) of colon tumor cells. Several AChE inhibitors dose-dependently suppressed colony formation of HTB-38 cells in soft agar. This effect of AChE was confirmed with HTB-38 cells stably overexpressing AChE. In contrast, cell proliferation was not altered by the effective doses of these chemical inhibitors or by transfected AChE. Protection from cell cycle arrest consecutive to cancer cell detachment may be conveyed by changes in cell-matrix interactions. Reflective of such changes, the AChE overexpressing cells adhered more strongly to Fibronectin than did the vector controls. The AChE-dependent adhesion was RGD-dependent and accompanied by increased c-Myb DNA-binding, suggesting that AChE upregulates an Integrin receptor via c-Myb. In support of these observations, we find AChE message and protein to be expressed in a large fraction of colon cancers and in all colon tumor cell lines analyzed, but only rarely in normal colon specimens. Our results imply a dual role for AChE in colon cancer. While the anti-apoptotic effects of AChE may be protective against early stages of tumorigenesis, this gene product may support the later stages of transformation by enhancing anchorage independent growth. The induction of Integrins could render the cells independent of microenvironmental cues and override cell cycle arrest after deadhesion.
Syed
Moyeenuddin
M
College of Pharmacy, University of Cincinnati Academic Health Center, 3225 Eden Avenue, Cincinnati, OH 45267-0004, USA.
Fenoglio-Preiser
Cecilia
C
Skau
Kenneth A
KA
Weber
Georg F
GF
D000110:Acetylcholinesterase / Q000502:physiology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D004247:DNA / Q000378:metabolism; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism
D005353:Fibronectins; D014157:Transcription Factors; D004247:DNA; D000110:Acetylcholinesterase