| RRC ID |
83463
|
| Author |
Arioka M, Yi W, Igawa K, Ishikane S, Takahashi-Yanaga F.
|
| Title |
Differentiation-inducing factor-1 inhibits EMT by proteasomal degradation of TAZ and YAP in cervical and colon cancer cell lines.
|
| Journal |
Eur J Pharmacol
|
| Abstract |
We previously reported differentiation-inducing factor-1 (DIF-1) activated glycogen synthase kinase-3 (GSK-3) in various mammalian cells. GSK-3 has been proposed to regulate a number of signaling pathway including TAZ/YAP signaling pathway. To clarify the effect of DIF-1 on TAZ/YAP signaling pathway, we examined whether DIF-1 affect the expression levels of TAZ and YAP. We found that DIF-1-induced proteasomal- and GSK-3-dependent degradation of both TAZ and YAP in human cervical cancer cell line HeLa in a time- and dose-dependent manner. As TAZ/YAP signaling pathway is well known to accelerate the epithelial-mesenchymal transition (EMT) of the cancer cell, we examined the effect of TAZ/YAP signaling pathway on EMT-related proteins. Knockdown of TAZ and YAP proteins by siRNA significantly reduced the expression of fibronectin, vimentin, and Snail. We also found that DIF-1 suppressed the expression levels of TAZ/YAP target gene products and EMT-related protein. Further, overexpression of TAZ and YAP attenuated the inhibitory effects of DIF-1 on these protein expressions. Migration and trans-well invasion assays revealed that DIF-1 significantly inhibited HeLa cell migration and invasion. DIF-1-induced proteasomal- and GSK-3-dependent degradation of TAZ and YAP proteins and inhibition of cell migration and invasion were also observed in human colon cancer cell line HCT-116. These results suggest that DIF-1 inhibits the TAZ/YAP signaling pathway via GSK-3 activation. Further, it has been suggested that the inhibition of EMT induced by DIF-1 is involved with the suppression of TAZ/YAP signaling pathway.
|
| Volume |
987
|
| Pages |
177184
|
| Published |
2025-1-15
|
| DOI |
10.1016/j.ejphar.2024.177184
|
| PII |
S0014-2999(24)00874-4
|
| PMID |
39645220
|
| MeSH |
Acyltransferases
Adaptor Proteins, Signal Transducing* / genetics
Adaptor Proteins, Signal Transducing* / metabolism
Cell Line, Tumor
Cell Movement / drug effects
Colonic Neoplasms* / metabolism
Colonic Neoplasms* / pathology
Epithelial-Mesenchymal Transition* / drug effects
Female
Gene Expression Regulation, Neoplastic / drug effects
Glycogen Synthase Kinase 3 / metabolism
HeLa Cells
Humans
Phosphoproteins / metabolism
Proteasome Endopeptidase Complex* / metabolism
Proteolysis* / drug effects
Signal Transduction / drug effects
Trans-Activators / genetics
Trans-Activators / metabolism
Transcription Factors* / genetics
Transcription Factors* / metabolism
Transcriptional Coactivator with PDZ-Binding Motif Proteins*
Uterine Cervical Neoplasms* / metabolism
Uterine Cervical Neoplasms* / pathology
YAP-Signaling Proteins* / metabolism
|
| IF |
3.263
|
| Resource |
| DNA material |
pFLAG-human yes-associated protein (YAP)1 (RDB13968) |
