The SIGnaling Network
Open Resource

Pathway ID: SIGNOR-HT

Description: Hepatocellular carcinoma (HCC) is one of the most common primary malignant neoplasma of the liver, anche one of the most widespread tumors in the world with a poor prognosis. Hepatocarcinogenesis is a complex and multistep process, infact numerous signaling modules are compromised and they’re the cause of the tumor’s development and progression. Among these, the pathways that involve growth factors, such us insulin-like growth factor (IGF) or hepatocyte growth factor (HGF) are frequently found mutated in patients. Also HCC is characterized by an aberrant activation of the WNT signaling pathway. In vitro study has demonstrated that NRF2 activation preserves tumor cells from toxic exposure to reactive oxygen species and subsequent death, infact this protein promotes the expression of the anti-oxidant response genes (NQO1, HMOX1 and GSTA1). TERT promoter mutation are involved at the last step of malignant transformation; infact 90% of human HCCs harbor an increased telomerase expression. Most of the time,TERT mutations are correlated with CTNNB1 mutations, suggesting cooperation between telomerase maintenance and b-catenin pathway in liver tumorigenesis. In particoular lots of patients with HCC have got inactivating mutations of ARID1A/B (3%-18%), underlining the key role of SWI/SNF chromatin remodeling complexes as tumor suppressors; on the other hand, towards the last stages of the disease, MYC and AKT activation partecipate to improve the proliferation (in approximately 50% of HCCs).

Curated by: Luana Licata