title: Cellular prion protein contributes to LS 174T colon cancer cell carcinogenesis by increasing invasiveness and resistance against doxorubicin-induced apoptosis.
abstract: As the cellular prion protein (PrP(C)) has been implicated in carcinogenesis, we aimed to investigate the effects of cancer cell-specific PrP(C) overexpression from the invasion, metastasis, and apoptosis aspects, by performing cell motility assays, cell proliferation assays under anchorage-dependent and anchorage-independent conditions, and apoptosis evasion when subjected to multiple anti-cancer drugs. Overexpression of PrP(C) in LS 174T was achieved by stable transfection. PrP(C) overexpression was shown to increase cell proliferation in anchorage-dependent and anchorage-independent manners, as shown by more viable cells in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, more colonies formed in soft agar assay and increased resistance to anoikis in poly-2-hydroxyethyl methacrylate-coated surface. PrP(C) overexpression also increased cell motility and invasiveness of LS 174T. Cell adhesion to extracellular matrix using collagen- and fibronectin-coated surfaces revealed increased cell attachment in LS 174T cells overexpressing PrP(C). Analysis of apoptotic and necrotic cells by propidium iodide/annexin V-fluorescein isothiocyanate microscopy and 7-amino-actinomycin D/annexin V-phycoerythrin flow cytometry revealed that PrP(C) overexpression attenuated doxorubicin-induced apoptosis. Human apoptosis antibody array with 35 apoptosis-related proteins revealed that three inhibitor of apoptosis proteins (IAPs)-survivin, X-linked inhibitor of apoptosis protein (XIAP), and cellular inhibitor of apoptosis protein-1 (cIAP-1)-were upregulated in LS 174T cells overexpressing PrP(C) in doxorubicin-induced apoptosis. In conclusion, the overexpression of PrP(C) could enhance the invasiveness and survival of LS 174T colorectal cancer cells, indicating that PrP(C) plays a role in colorectal cancer biology.
authors.affiliation: Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Perak Campus, Jalan Universiti, Bandar Barat, 31900, Kampar, Perak, Malaysia.
authors.forename: Cornelius Kwang-Lee
authors.initials: CK
authors.lastname: Chieng
authors.affiliation: Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Perak Campus, Jalan Universiti, Bandar Barat, 31900, Kampar, Perak, Malaysia. sayyh@utar.edu.my.
authors.forename: Yee-How
authors.initials: YH
authors.lastname: Say
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009361:Neoplasm Invasiveness; D018621:PrPC Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D018621:PrPC Proteins; D004317:Doxorubicin
keywords: Apoptosis; Cellular prion protein; Colon cancer; Invasion; Metastasis