title: EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis.
abstract: Epithelial-mesenchymal transition (EMT) is a crucial mechanism for the acquisition of migratory and invasive capabilities by epithelial cancer cells. By conducting quantitative proteomics in experimental models of human prostate cancer (PCa) metastasis, we observed strikingly decreased expression of EPLIN (epithelial protein lost in neoplasm; or LIM domain and actin binding 1, LIMA-1) upon EMT. Biochemical and functional analyses demonstrated that EPLIN is a negative regulator of EMT and invasiveness in PCa cells. EPLIN depletion resulted in the disassembly of adherens junctions, structurally distinct actin remodeling and activation of β-catenin signaling. Microarray expression analysis identified a subset of putative EPLIN target genes associated with EMT, invasion and metastasis. By immunohistochemistry, EPLIN downregulation was also demonstrated in lymph node metastases of human solid tumors including PCa, breast cancer, colorectal cancer and squamous cell carcinoma of the head and neck. This study reveals a novel molecular mechanism for converting cancer cells into a highly invasive and malignant form, and has important implications in prognosis and treating metastasis at early stages.
authors.affiliation: Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: A O
authors.initials: AO
authors.lastname: Osunkoya
authors.forename: S
authors.initials: S
authors.lastname: Iqbal
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Müller
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Josson
authors.forename: I M
authors.initials: IM
authors.lastname: Coleman
authors.forename: P S
authors.initials: PS
authors.lastname: Nelson
authors.forename: Y A
authors.initials: YA
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: D M
authors.initials: DM
authors.lastname: Shin
authors.forename: F F
authors.initials: FF
authors.lastname: Marshall
authors.forename: O
authors.initials: O
authors.lastname: Kucuk
authors.forename: L W K
authors.initials: LW
authors.lastname: Chung
authors.forename: H E
authors.initials: HE
authors.lastname: Zhau
authors.forename: D
authors.initials: D
authors.lastname: Wu
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; C403263:LIMA1 protein, human; D009363:Neoplasm Proteins; D051176:beta Catenin