Cellular prion protein contributes to LS 174T colon cancer cell carcinogenesis by increasing invasiveness and resistance against doxorubicin-induced apoptosis

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Abstract
As the cellular prion protein (PrPC) has been implicated in carcinogenesis, we aimed to investigate the effects of cancer cell-specific PrPC 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 PrPC in LS 174T was achieved by stable transfection. PrPC 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. PrPC 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 PrPC. 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 PrPC 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 PrPC in doxorubicin-induced apoptosis. In conclusion, the overexpression of PrPC could enhance the invasiveness and survival of LS 174T colorectal cancer cells, indicating that PrPC plays a role in colorectal cancer biology.

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