title: Phosphatase and Tensin Homolog (PTEN) Represses Colon Cancer Progression through Inhibiting Paxillin Transcription via PI3K/AKT/NF-κB Pathway.
abstract: The tumor suppressor gene phosphatase and tensin homolog (PTEN) is frequently mutated in colon cancer. However, the potential contribution of loss of PTEN to colon cancer progression remains unclear. In this study, we demonstrated that PTEN overexpression or knockdown in Lovo colon cancer cells decreased or increased paxillin expression, respectively. Moreover, paxillin reversed PTEN-mediated inhibition of Lovo cell invasion and migration. Overexpression of PTEN in an orthotropic colon cancer nude mice model inhibited tumor formation and progression. In addition, PTEN protein level was negatively correlated with that of paxillin in human colon cancer tissues. Mechanistically, we identified three NF-κB binding sites on paxillin promoter and confirmed that paxillin was a direct transcriptional target of NF-κB. Our findings reveal a novel mechanism by which PTEN inhibits the progression of colon cancer by inhibiting paxillin expression downstream of PI3K/AKT/NF-κB pathway. Thereby, PTEN/PI3K/AKT/NF-κB/paxillin signaling cascade is an attractive therapeutic target for colon cancer progression.
authors: From the Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan and the Departments of Gastroenterology and.
authors: Ling-Li
authors: LL
authors: Zhang
authors: From the Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan and.
authors: Gang-Gang
authors: GG
authors: Mu
authors: From the Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan and.
authors: Qian-Shan
authors: QS
authors: Ding
authors: From the Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan and.
authors: Yan-Xia
authors: YX
authors: Li
authors: Neurology, the First Affiliated Hospital of Zhengzhou University, 450000 Henan province, China.
authors: Yun-bo
authors: YB
authors: Shi
authors: From the Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan and.
authors: Jin-Fen
authors: JF
authors: Dai
authors: From the Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan and yhgwhu@gmail.com.
authors: Hong-Gang
authors: HG
authors: Yu
mesh_terms: D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D051419:Paxillin / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; C496061:PXN protein, human; D051419:Paxillin; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: NF-kappa B (NF-KB); colon cancer; metastasis; paxillin; phosphatase and tensin homolog (PTEN); progression; transcription