title: From cirrhosis to hepatocellular carcinoma: new molecular insights on inflammation and cellular senescence.
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.
authors.affiliation: Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Ramakrishna
authors.affiliation: Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Rastogi
authors.affiliation: Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Trehanpati
authors.affiliation: Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Bijoya
authors.initials: B
authors.lastname: Sen
authors.affiliation: Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Khosla
authors.affiliation: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sarin
keywords: Cellular senescence; Cirrhosis; Genetic/Epigenetic landscape; Hepatocellular carcinoma; Inflammasomes