title: Knockdown of integrin α3β1 expression induces proliferation and migration             of non-small cell lung cancer cells.
abstract: Integrin α3β1 is expressed on many types of cancer cells and can regulate             tumor growth and progression. In the present study, we examined the roles and             molecular mechanism of integrin α3β1 in modulating cell proliferation and migration             of p53-deficient non-small cell lung cancer (NSCLC) cells. Reduced expression             of integrin α3 by RNA silencing clearly induces cell proliferation and migration             in H1299 cells, compared with those in control cells. Enhanced proliferation in             integrin α3-silenced cells is mediated by upregulation and nuclear localization             of cyclin-dependent kinases, and these effects require the activation of Akt and             ERK as evidenced by treatment with LY294002 and PD98059, respectively. Furthermore,             suppression of integrin α3 expression induces the expression of nuclear factor-κB             and Bcl-2 as well as epidermal growth factor receptor, which are positively correlated             with cell proliferation and survival. In contrast, increase in cell migration             of integrin α3-silenced cells is found to be independent of Akt or ERK signaling             pathways. Collectively, these findings suggest that integrin α3β1 plays pivotal             roles in regulating cell proliferation and migration that enhance the invasive             type of p53-deficient NSCLC cells.
authors.affiliation: Quality Management Department, Hugel Inc., Chuncheon 200-821,                     Republic of Korea.
authors.forename: Hyun Jae
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Young-Rak
authors.initials: YR
authors.lastname: Cho
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Joo
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D018844:Cyclin-Dependent Kinases; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D039201:Integrin alpha3beta1 / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency; D015854:Up-Regulation
chemical_list: D039201:Integrin alpha3beta1; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D018844:Cyclin-Dependent Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9