Paternally Expressed Gene 10 (PEG10) Promotes Growth, Invasion and Survival of Bladder Cancer.

Gleave, Martin E; Kawai, Yoshihisa; Imada, Kenjiro; Akamatsu, Shusuke; Zhang, Fan; Seiler, Roland; Hayashi, Tetsutaro; Leong, Jeffrey; Beraldi, Eliana; Saxena, Neetu; Kretschmer, Alexander; Oo, Htoo Zarni; Contreras-Sanz, Alberto; Matsuyama, Hideyasu; Lin, Dong; Fazli, Ladan; Collins, Colin C; Wyatt, Alexander W; Black, Peter C (2020). Paternally Expressed Gene 10 (PEG10) Promotes Growth, Invasion and Survival of Bladder Cancer. Molecular cancer therapeutics, 19(10), pp. 2210-2220. American Association for Cancer Research AACR 10.1158/1535-7163.MCT-19-1031

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Paternally Expressed Gene 10 (PEG10) has been associated with neuroendocrine (NE)-muscle-invasive bladder cancer (MIBC), a subtype of the disease with the poorest survival. In this work, we further characterized the expression pattern of PEG10 in TCGA database of 412 MIBC pateints, and found that, compared to other subtypes, PEG10 mRNA level was enhanced in NE-like MIBC and highly correlats with other NE markers. PEG10 protein level also associated with NE markers in a tissue microarray (TMA) of 82 cases. In bladder cancer cell lines, PEG10 expression was induced in drug-resistant compared to parental cells, and knocking-down of PEG10 re-sensitized cells to chemotherapy. Loss of PEG10 increased protein levels of cell cycle regulators p21 and p27 and delayed G1/S transition, while over-expression of PEG10 enhanced cancer cell proliferation. PEG10 silencing also lowered levels of SLUG and SNAIL, leading to reduced invasion and migration. In an orthotopic bladder cancer model, systemic treatment with PEG10 antisense oligonucleotide delayed progression of T24 xenografts. In summary, elevated expression of PEG10 in MIBC may contribute to the disease progression by promoting survival, proliferation and metastasis. Targeting PEG10 is a novel potential therapeutic approach for a subset of bladder cancers.

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