PMID: 32509204Jun 9, 2020Paper

Dedifferentiation of hepatocellular carcinoma: molecular mechanisms and therapeutic implications

American Journal of Translational Research
Jiashuo ChaoHongcheng Sun

Abstract

Hepatocellular carcinoma (HCC) is a common cancer with high morbidity and mortality. Poorer differentiation status indicates worse prognosis of HCC patients. Regain of better differentiation status may improve the prognosis. Differentiation therapy for HCC is based on the fact that agents may reverse the dedifferentiation process from hepatocytes to HCC cells and thus improve tumor differentiation status. Reversal of progenitor-like property and restoration of hepatic characteristics are main objectives of HCC differentiation therapy. Comprehending the mechanisms of HCC dedifferentiation provides ideas for drug design. Diverse dysregulated molecules and signalings cooperatively cause HCC dedifferentiation. Dysregulation of liver enriched transcription factors, especially hepatocyte nuclear factor 4α, was a critical determinant of HCC dedifferentiation. Aberrant pivotal signaling molecules such as transforming factor-β, β-catenin and Yes-associated protein caused disordered signalings, which promoted HCC dedifferentiation. Loss of epithelial morphology during epithelial-mesenchymal transition (EMT) concurred with HCC dedifferentiation. Some EMT-related molecules exerted double-sided role in concurrently inducing EMT and HCC dedi...Continue Reading

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