From Cirrhosis to Hepatocellular Carcinoma: New Molecular Insights on Inflammation and Cellular Senescence
Year: 2013
Type: review
Abstract: Sequential progression from chronic liver disease to fibrosis and to cirrhosis culminates in neoplasia in hepatocellular carcinoma (HCC). The preneoplastic setting of the cirrhotic background provides a conducive environment for cellular transformation. The role of classical inflammation in cirrhosis is widely known, but the exact mechanism linking inflammation and cancer remains elusive. Recent studies have elucidated roles for NF-κB, STAT3 and JNK as possible missing links. In addition, the "inflammasome" (a multiprotein complex and sensor of cellular damage) is a recently identified player in this field. The hallmarks of cirrhosis include necroinflammation, deposition of extracellular matrix and shortening of telomeres, leading to senescence and regeneration. Additionally, the accumulation of genetic/epigenetic changes propels atypical cells toward a malignant phenotype. This review provides recent information on the classical inflammatory pathway, together with a spotlight on inflammasomes and the immunomodulatory role of cellular senescence during the progression from cirrhosis to HCC. Moreover, lacunae in the current knowledge were identified and key questions raised on whether the observed adaptive responses are beneficial or detrimental to tissue homeostasis in a complex organ like liver.
Source: Liver Cancer
DOI: 10.1159/000343852
Institution: Institute of Liver and Biliary Sciences
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,590
OpenAlex ID: W1982129504