title: Krüppel-like factor 4 negatively regulates β-catenin expression and             inhibits the proliferation, invasion and metastasis of gastric cancer.
abstract: Krüppel-like factor 4 (KLF4) is a zinc-finger protein that plays an important role in the progression of gastric carcinoma. The abnormal activation of β-catenin frequently occurs in gastric cancer and has been associated with the promotion of tumor growth, invasion and metastasis. However, the potential interaction between KLF4 and β-catenin during gastric cancer development is unknown. In this study, a lentiviral KLF4 expression vector was constructed and utilized to transfect the human gastric cancer cell lines, SGC-7901, BGC-823, MKN-28 and MKN-45. KLF4 and β-catenin expression levels were measured by quantitative real-time RT-PCR and western blot analysis. Cell proliferation, colony formation and invasive potential were determined in the KLF4-transfected gastric cancer cells. The expression of E-cadherin and matrix metallopeptidase 2 (MMP2) was determined by western blot analysis. The overexpression of KLF4 significantly inhibited the expression of β-catenin in the MKN-45 gastric cancer cells. The restored expression of KLF4 suppressed proliferation, colony formation and inhibited the invasion and metastatic properties of MKN-45 gastric cancer cells. Furthermore, the forced expression of KLF4 in gastric tumor cell lines restored E-cadherin expression and inhibited MMP2 expression. Consistent with the in vitro findings, the enforced expression of the KLF4 gene in MKN-45 gastric carcinoma cells by lentiviral vector-mediated gene transfer effectively suppressed tumor growth in vivo. Our results show that KLF4 inhibits β-catenin expression and regulates the β-catenin-mediated biological behaviors of gastric cancer cells. The modulation of KLF4 expression may represent a novel therapeutic approach for β-catenin-driven malignancies.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital                     of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Neng
authors.initials: N
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Leiyuan
authors.initials: L
authors.lastname: Shuai
authors.forename: Lang
authors.initials: L
authors.lastname: Zha
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic; D047368:Tumor Burden; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015820:Cadherins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D011994:Recombinant Proteins; D051176:beta Catenin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2