Reference - Detail
| RRC ID | 52183 |
|---|---|
| Author | Gen Y, Yasui K, Kitaichi T, Iwai N, Terasaki K, Dohi O, Hashimoto H, Fukui H, Inada Y, Fukui A, Jo M, Moriguchi M, Nishikawa T, Umemura A, Yamaguchi K, Konishi H, Naito Y, Itoh Y. |
| Title | ASPP2 suppresses invasion and TGF-β1-induced epithelial-mesenchymal transition by inhibiting Smad7 degradation mediated by E3 ubiquitin ligase ITCH in gastric cancer. |
| Journal | Cancer Lett |
| Abstract |
ASPP2 regulates cell polarity and cell-cell adhesion by binding to, and co-localizing with PAR3 at tight junctions. Here we show a novel role of ASPP2 in suppressing gastric cancer (GC) invasiveness. Immunoprecipitation and immunofluorescence analyses showed that ASPP2 promoted the recruitment of PAR3 to cell-cell junctions in GC cells. Diminished expression of ASPP2 and loss of junctional PAR3 localization were significantly associated with diffuse-type histology, deeper invasion depth, positive peritoneal dissemination and worse prognosis in primary GC. ASPP2 suppressed migration and invasion of GC cells in vitro and peritoneal dissemination of GC cells in vivo in a mouse model. ASPP2 suppressed epithelial-mesenchymal transition (EMT) induced by TGF-β1-Smad2/3 signaling in GC cells through suppression of the degradation of Smad7, a negative regulator of TGF-β1-Smad2/3 signaling, by interacting with the E3 ubiquitin ligase ITCH. In conclusion, ASPP2 suppresses invasion, peritoneal dissemination and TGF-β1-induced EMT by inhibiting Smad7 degradation mediated by ITCH. |
| Volume | 398 |
| Pages | 52-61 |
| Published | 2017-7-10 |
| DOI | 10.1016/j.canlet.2017.04.002 |
| PII | S0304-3835(17)30232-X |
| PMID | 28400336 |
| MeSH | Adaptor Proteins, Signal Transducing Animals Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism* Cell Cycle Proteins / metabolism Cell Line, Tumor Cell Movement* / drug effects Epithelial-Mesenchymal Transition* / drug effects Humans Intercellular Junctions / metabolism Intercellular Junctions / pathology Membrane Proteins / metabolism Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness Peritoneal Neoplasms / enzymology* Peritoneal Neoplasms / genetics Peritoneal Neoplasms / secondary Protein Stability Proteolysis Repressor Proteins / metabolism* Signal Transduction Smad2 Protein / metabolism Smad3 Protein / metabolism Smad7 Protein / metabolism* Stomach Neoplasms / enzymology* Stomach Neoplasms / genetics Stomach Neoplasms / pathology Time Factors Transfection Transforming Growth Factor beta1 / metabolism* Transforming Growth Factor beta1 / pharmacology Ubiquitin-Protein Ligases / metabolism* Ubiquitination |
| IF | 7.36 |
| Times Cited | 13 |
| Resource | |
| Human and Animal Cells | MKN7(RCB0999) MKN45(RCB1001) MKN74(RCB1002) Kato III(RCB2088) NUGC-4(RCB1939) |