RRC ID 1432
著者 Hayashida Y, Honda K, Idogawa M, Ino Y, Ono M, Tsuchida A, Aoki T, Hirohashi S, Yamada T.
タイトル E-cadherin regulates the association between beta-catenin and actinin-4.
ジャーナル Cancer Res
Abstract The E-cadherin/catenin system acts as an invasion suppressor of epithelial malignancies. This invasion suppressive activity seems be mediated not only by the cell adhesive activity of E-cadherin but by other undetermined signaling pathways elicited by beta-catenin. In fact, cancer cells that have infiltrated the stroma reduce the expression of E-cadherin and accumulate beta-catenin. We attempted to identify the alternative partner proteins that make complexes with beta-catenin in the absence of E-cadherin. An approximately 100-kDa protein was constantly coimmunoprecipitated with beta-catenin from SW480 colorectal cancer cells, which lack the expression of E-cadherin, and was identified as actinin-4 by mass spectrometry. Transfection of E-cadherin cDNA suppressed the association between beta-catenin and actinin-4. Inhibition of E-cadherin by RNA interference transferred the beta-catenin and actinin-4 proteins into the membrane protrusions of DLD-1 cells. Immunofluorescence histochemistry of clinical colorectal cancer specimens showed that the beta-catenin and actinin-4 proteins were colocalized in colorectal cancer cells infiltrating the stroma. We reported previously that overexpression of actinin-4 induces cell motility and specifically promotes lymph node metastasis by colorectal cancer. The association between beta-catenin and actinin-4 and its regulation by E-cadherin may represent a novel molecular link connecting cell adhesion and motility. Shutting down the signals mediating this association may be worth considering as a therapeutic approach to cancer invasion and metastasis.
巻・号 65(19)
ページ 8836-45
公開日 2005-10-1
DOI 10.1158/0008-5472.CAN-05-0718
PII 65/19/8836
PMID 16204054
MeSH Actinin / metabolism* Actins / metabolism Amino Acid Sequence Cadherins / biosynthesis Cadherins / genetics Cadherins / metabolism* Cell Line, Tumor Cell Movement / physiology Cell Nucleus / metabolism Colorectal Neoplasms / genetics Colorectal Neoplasms / metabolism Colorectal Neoplasms / pathology Humans Laminin Microfilament Proteins / metabolism* Molecular Sequence Data Neoplasm Invasiveness Neoplasm Metastasis Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology Stromal Cells / pathology Transfection beta Catenin / biosynthesis beta Catenin / metabolism*
IF 9.727
引用数 87
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 COLO-320(RCB1193)