title: Smad4 restoration leads to a suppression of Wnt/beta-catenin signaling activity and migration capacity in human colon carcinoma cells.
abstract: Recent studies have reported that Smad4 has a TGF-beta-independent function as a tumor suppressor in cooperating with beta-catenin/Lef to regulate target gene expression. The objective of this research was to study the role of Smad4 in colon cancer migration and its potential mechanism. In our study, stable colon cancer cells that have increased Smad4 expression were created using a eukaryotic vector containing Smad4-pcDNA3.1(+). Smad4 restoration directly suppressed the Wnt/beta-catenin signal activity in SW480 cells by down-regulating beta-catenin expression and altering its localization from cytoplasm and nucleus to the plasma membrane. Up-regulation of Smad4 also increased the expression of E-cadherin and decreased the transcriptional activity of beta-catenin/Tcf target genes, such as claudin-1 and MMP-7. SW480 cells with increased Smad4 expression had decreased in vitro cell migration. The data suggested that restoration of Smad4 in Smad4-deficient cells may provide a potential therapeutic strategy for intervention of colon cancer migration and metastasis.
authors.affiliation: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou Road 1838, Guangzhou 510515, Guangdong Province, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Tian
authors.forename: Hao
authors.initials: H
authors.lastname: Du
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Fu
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein; D051153:Wnt Proteins; D051176:beta Catenin