PTEN inhibits the invasion and metastasis of gastric cancer via downregulation of FAK expression.
The tumor suppressor gene phosphatase and tensin homolog (PTEN) is essential in inhibiting tumor growth and metastasis. However, the mechanism by which PTEN restricts gastric cancer progression and metastasis remains largely elusive. Here we demonstrated that PTEN overexpression or knockdown in gastric cancer cells led to the downregulation or upregulation of focal adhesion kinase (FAK), and decreased or increased cell invasion, respectively. Moreover, FAK overexpression could rescue the inhibition of cell invasion by PTEN. These results were further confirmed in orthotropic gastric cancer nude mice model. In addition, in human gastric cancer tissues, PTEN protein level was conversely correlated with FAK protein level. Mechanistically, we found that PTEN inhibited PI3K/NF-κB pathway and inhibited the DNA binding of NF-κB on FAK promoter. Taken together, our data reveal a novel mechanism that PTEN inhibits the growth and invasion of gastric cancer via the downregulation of FAK expression and suggest that exploiting PTEN/PI3K/NF-κB/FAK axis is a promising approach to treat gastric cancer metastasis.
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China; Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China.
Ling-Li
LL
Zhang
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China; Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China.
Jie
J
Liu
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China; Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China.
Shen
S
Lei
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China; Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China.
Jun
J
Zhang
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China; Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China.
Wei
W
Zhou
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China; Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China. Electronic address: yhgwhu@gmail.com.
Hong-Gang
HG
Yu
D019943:Amino Acid Substitution; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D014183:Transplantation, Heterologous
D016328:NF-kappa B; D058539:Phosphatidylinositol 3-Kinase; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051059:PTEN Phosphohydrolase
Focal adhesion kinase; Migration; Transcription; Tumorigenicity