title: The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice.
abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Yunnan, China.
authors.forename: Miaojun
authors.initials: M
authors.lastname: Han
authors.forename: Hailun
authors.initials: H
authors.lastname: Wang
authors.forename: Hua-Tang
authors.initials: HT
authors.lastname: Zhang
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Han
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005353:Fibronectins / Q000737:chemistry; D022001:Focal Adhesions / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D054731:PDZ Domains; D034622:RNA Interference; D051176:beta Catenin / Q000378:metabolism
chemical_list: D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; C421249:TAX1BP3 protein, human; D051176:beta Catenin