| RRC ID |
72126
|
| 著者 |
Fujibayashi E, Mukai S, Torigata K, Ando Y, Uchihashi T, Nozaki M, Tanaka S, Okada M, Kogo M, Nojima H, Yabuta N.
|
| タイトル |
LATS kinases and SLUG regulate the transition to advanced stage in aggressive oral cancer cells.
|
| ジャーナル |
Sci Rep
|
| Abstract |
The epithelial-to-mesenchymal transition (EMT) is a critical process by which cancer cells acquire malignant features. However, the molecular mechanism and functional implications of EMT and the mesenchymal-to-epithelial transition (MET) in tumor progression remain elusive. In this study, we established two aggressive cancer cell lines from the human oral cancer cell line SAS, mesenchymal-like SAS-m4 and epithelial-like SAS-δ. SAS-δ is a revertant cell obtained by inducing MET in SAS-m4. SAS-δ, but not SAS-m4, exhibited abnormal cell growth, including piled-up overgrowth and invasive tumor formation in the tongues of nude mice, suggesting that SAS-δ represented more advanced cancer cells than the parental SAS cells. EMT-related transcriptional factor SLUG is phosphorylated at T208 and partly stabilized by the Hippo pathway kinases, LATS1 and LATS2. Depletion of SLUG promoted the invasive activity of SAS-δ by increasing the protein levels of LATS1/2 and the proportion of the phosphorylated form among total SLUG protein. Our results suggest that the LATS1/2-SLUG axis regulates the transition of SAS cells to the advanced stage via repeated switching between EMT and MET. Therefore, an anti-SLUG-pT208 antibody would be valuable not alone as a malignant tumor marker antibody but also as a prognostic tool for patients with malignant disease.
|
| 巻・号 |
12(1)
|
| ページ |
12363
|
| 公開日 |
2022-7-20
|
| DOI |
10.1038/s41598-022-16667-5
|
| PII |
10.1038/s41598-022-16667-5
|
| PMID |
35859006
|
| PMC |
PMC9300623
|
| MeSH |
Animals
Cell Line, Tumor
Humans
Long-Acting Thyroid Stimulator*
Mice
Mice, Nude
Mouth Neoplasms* / genetics
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Snail Family Transcription Factors / genetics
Snail Family Transcription Factors / metabolism*
Tumor Suppressor Proteins
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
SAS(RCB1974) |
