[Dysfunction of E-cadherin-catenin system in invasion and metastasis of colorectal cancer].
The E-cadherin-mediated cell adhesion system is now considered to be an "invasion suppressor system" in cancer cells. Dysfunction of the E-cadherin system due to mutations of the genes of E-cadherin and catenins has not been reported in colorectal cancer. Histologically, well-differentiated colorectal cancer cells are found to be scattered at the invasive front in primary lesions and form glands again in metastatic sites. We have reported the association and presence of signal transduction between c-erbB-2/epidermal growth factor receptor (EGF-R) and beta-catenin in human cancer cells. This temporal dysfunction of the E-cadherin system observed in colon cancers may be caused by tyrosine phosphorylation of beta-catenin through activated receptor-type tyrosine kinases. Overexpression of EGF-R and tyrosine phosphorylation of beta-catenin are often observed in "focal dedifferentiated cells" at the invasive front of colorectal cancers. In addition, beta-catenin expression is regulated by the APC tumor suppressor gene product. Thus the E-cadherin-catenin system may play important roles not only in invasion and metastasis but also in the carcinogenesis of colorectal cancer.
Maruyama
K
K
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Ochiai
A
A
Nakamura
S
S
Baba
S
S
Hirohashi
S
S
D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction; D015534:Trans-Activators; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D051176:beta Catenin; C495270:CTNNB1 protein, human