Metformin reverses a precancerous niche featuring cytoplasmic p21WAF1/CIP1-expressing hepatocytes and prevents hepatocellular carcinoma development
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ABSTRACT: Prevention and treatment options for hepatocellular carcinoma (HCC) are presently limited, underscoring the necessity for elucidating molecular mechanisms underlying HCC development and identifying new prevention and therapeutic targets. We demonstrate a unique precancerous niche that features enhanced p53 pathway, aberrant cytoplasmic p21WAF1/CIP1-expressing hepatocytes, and increased CD8+ T lymphocyte and macrophage infiltration in the livers of Ncoa5+/- mouse model of HCC. Metformin treatment reverses these precancerous features and profoundly reduces tumor incidence. Our data also reveal that a subset of HCC patients with a similar precancerous niche in the adjacent noncancerous livers had a relatively poor prognosis. Our study suggests a perceptible hepatic niche predisposing to HCC development and uncovers new actions of metformin in the prevention and treatment of HCC.
ORGANISM(S): Mus musculus
PROVIDER: GSE110524 | GEO | 2020/03/28
REPOSITORIES: GEO
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