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TMPRSS4 promotes invasiveness of human gastric cancer cells through activation of NF-κB/MMP-9 signaling.
Jin, Jie; Shen, Xian; Chen, Lei; Bao, Luo-wen; Zhu, Li-ming.
Afiliación
  • Jin J; Department of Digestive Diseases, Wenzhou Central Hospital, Wenzhou, China.
  • Shen X; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Chen L; Department of Surgery, Wenzhou Central Hospital, Wenzhou, China.
  • Bao LW; Department of Digestive Diseases, Wenzhou Central Hospital, Wenzhou, China.
  • Zhu LM; Department of Digestive Diseases, Wenzhou Central Hospital, Wenzhou, China. Electronic address: lim_zhu_2015@163.com.
Biomed Pharmacother ; 77: 30-6, 2016 Feb.
Article en En | MEDLINE | ID: mdl-26796262
Transmembrane protease serine 4 (TMPRSS4) is a type-II transmembrane serine protease that is frequently upregulated in human cancers. However, little is known about the biological roles of TMPRSS4 in gastric cancer. In this study, we examined the effect of TMPRSS4 on gastric cancer cell proliferation, migration, and invasion. The expression and secretion of matrix metalloproteinase-9 (MMP-9) and activation of nuclear factor-κB (NF-κB) were determined. The involvement of NF-κB/MMP-9 signaling was checked. Our data showed that TMPRSS4 silencing significantly (P<0.05) reduced the migration and invasion of AGS and MKN-45 gastric cancer cells, without affecting cell proliferation. Overexpression of TMPRSS4 significantly promoted cell migration and invasion. The expression and secretion of MMP-9 was significantly (P<0.05) enhanced in TMPRSS4-overexpressing cells. TMPRSS4-overexpressing cells had a significantly (P<0.05) lower level of IκBα and higher level of nuclear NF-κB. Luciferase reporter assay confirmed that overexpression of TMPRSS4 resulted in a 3-5-fold increase in NF-κB-dependent luciferase activity. Downregulation of MMP-9 significantly (P<0.05) reversed the invasiveness of gastric cancer cells induced by TMPRSS4 overexpression. Moreover, pharmacological inhibition of NF-κB attenuated the invasion of TMPRSS4-overexpressing cells and the expression of MMP-9. Upregulation of TMPRSS4 enhances the invasiveness of gastric cancer cells, largely through activation of NF-κB and induction of MMP-9 expression. Our study provides the rationale for targeting TMPRSS4 in the treatment of gastric cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Serina Endopeptidasas / FN-kappa B / Metaloproteinasa 9 de la Matriz / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Biomed Pharmacother Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Serina Endopeptidasas / FN-kappa B / Metaloproteinasa 9 de la Matriz / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Biomed Pharmacother Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia