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

Authors :
Kawai Y
Imada K
Akamatsu S
Zhang F
Seiler R
Hayashi T
Leong J
Beraldi E
Saxena N
Kretschmer A
Oo HZ
Contreras-Sanz A
Matsuyama H
Lin D
Fazli L
Collins CC
Wyatt AW
Black PC
Gleave ME
Source :
Molecular cancer therapeutics [Mol Cancer Ther] 2020 Oct; Vol. 19 (10), pp. 2210-2220. Date of Electronic Publication: 2020 Aug 26.
Publication Year :
2020

Abstract

Paternally expressed gene 10 ( PEG10 ) has been associated with neuroendocrine 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 The Cancer Genome Atlas database of 412 patients with MIBC, and found that, compared with other subtypes, PEG10 mRNA level was enhanced in neuroendocrine-like MIBC and highly correlated with other neuroendocrine markers. PEG10 protein level also associated with neuroendocrine markers in a tissue microarray of 82 cases. In bladder cancer cell lines, PEG10 expression was induced in drug-resistant compared with parental cells, and knocking down of PEG10 resensitized cells to chemotherapy. Loss of PEG10 increased protein levels of cell-cycle regulators p21 and p27 and delayed G <subscript>1</subscript> -S-phase transition, while overexpression 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.<br /> (©2020 American Association for Cancer Research.)

Details

Language :
English
ISSN :
1538-8514
Volume :
19
Issue :
10
Database :
MEDLINE
Journal :
Molecular cancer therapeutics
Publication Type :
Academic Journal
Accession number :
32847979
Full Text :
https://doi.org/10.1158/1535-7163.MCT-19-1031