論文 - 詳細
| RRC ID | 62768 |
|---|---|
| 著者 | Shin WS, Hong Y, Lee HW, Lee ST. |
| タイトル | Catalytically defective receptor protein tyrosine kinase PTK7 enhances invasive phenotype by inducing MMP-9 through activation of AP-1 and NF-κB in esophageal squamous cell carcinoma cells. |
| ジャーナル | Oncotarget |
| Abstract |
Protein tyrosine kinase 7 (PTK7), a member of the catalytically defective receptor protein tyrosine kinase family, is upregulated in various cancers including esophageal squamous cell carcinoma (ESCC). Here, we have explored the molecular mechanism of PTK7-dependent invasiveness in ESCC cells. PTK7 knockdown reduced gelatin degradation and MMP-9 secretion in cultures of ESCC TE-10 cells, and showed reduced levels of MMP9 mRNA using real-time RT-PCR and luciferase reporter assays. PTK7 knockdown decreased not only phosphorylation of NF-κB, IκB, ERK, and JNK, but also nuclear localization of NF-κB and AP-1 consisting of c-Fos and c-Jun. Activation of AP-1 and NF-κB requires PTK7-mediated activation of tyrosine kinases, including Src. In addition, NF-κB activation by PTK7 involves the PI3K/Akt signaling pathway. PTK7-mediated upregulation of MMP9 was also observed in other ESCC cell lines and in three-dimensional cultures of TE-10 cells. Moreover, MMP-9 expression positively correlated with PTK7 expression in ESCC tumor tissue. These findings demonstrate that PTK7 upregulates MMP9 through activation of AP-1 and NF-κB and, thus increases invasive properties of ESCC cells. |
| 巻・号 | 7(45) |
| ページ | 73242-73256 |
| 公開日 | 2016-11-8 |
| DOI | 10.18632/oncotarget.12303 |
| PII | 12303 |
| PMID | 27689325 |
| PMC | PMC5341976 |
| MeSH | Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology* Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism* Cell Line, Tumor Esophageal Neoplasms / genetics Esophageal Neoplasms / metabolism* Esophageal Neoplasms / pathology* Esophageal Squamous Cell Carcinoma Gene Knockdown Techniques Humans Immunohistochemistry Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism* NF-kappa B / metabolism* Neoplasm Invasiveness Phenotype Phosphatidylinositol 3-Kinases / metabolism Phosphorylation Proteolysis Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism* Signal Transduction Transcription Factor AP-1 / metabolism* Transcription, Genetic src-Family Kinases / metabolism |
| IF | 5.168 |
| リソース情報 | |
| ヒト・動物細胞 | TE-5(RCB1949) TE-6(RCB1950) TE-9(RCB1988) TE-10(RCB2099) TE-11(RCB2100) TE-14(RCB2101) |