Nectin-4 and p95-ErbB2 cooperatively regulate Hippo signaling-dependent SOX2 gene expression, enhancing anchorage-independent T47D cell proliferation
| Autor: | Kiyohito Mizutani, Takeshi Kameyama, Shin Kedashiro, Yoshimi Takai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
MST1
Receptor ErbB-2 Science Breast Neoplasms Protein Serine-Threonine Kinases Biochemistry Article Phosphatidylinositol 3-Kinases Cytosol SOX2 Cell Line Tumor Gene expression Cell Adhesion Humans Hippo Signaling Pathway RNA Small Interfering skin and connective tissue diseases neoplasms Cell Proliferation Cell Nucleus Multidisciplinary DNA synthesis Cell growth Chemistry Gene Expression Profiling SOXB1 Transcription Factors Oncogenes Cell biology Gene Expression Regulation Neoplastic Hippo signaling Cell culture Cancer cell Medicine Female Cell Adhesion Molecules Plasmids Signal Transduction |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Nectin-4, upregulated in various cancer cells, cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, p95-ErbB2 and ErbB2∆Ex16, enhancing DNA synthesis through the PI3K-AKT signaling in human breast cancer T47D cells in an adherent culture. We found here that nectin-4 and p95-ErbB2, but not nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively enhanced SOX2 gene expression and cell proliferation in a suspension culture. This enhancement of T47D cell proliferation in a suspension culture by nectin-4 and p95-ErbB2 was dependent on the SOX2 gene expression. In T47D cells, nectin-4 and any one of p95-ErbB2, ErbB2, or ErbB2∆Ex16 cooperatively activated the PI3K-AKT signaling, known to induce the SOX2 gene expression, to similar extents. However, only a combination of nectin-4 and p95-ErbB2, but not that of nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively enhanced the SOX2 gene expression. Detailed studies revealed that only nectin-4 and p95-ErbB2 cooperatively activated the Hippo signaling. YAP inhibited the SOX2 gene expression in this cell line and thus the MST1/2-LATS1/2 signaling-mediated YAP inactivation increased the SOX2 gene expression. These results indicate that only the combination of nectin-4 and p95-ErbB2, but not that of nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively regulates the Hippo signaling-dependent SOX2 gene expression, enhancing anchorage-independent T47D cell proliferation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |