| 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) |
