Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

Abstract

The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated. Autophagy and apoptosis are two important cellular pathways that are critical for cell survival or death. The balance between apoptosis and autophagy regulates liver cell turnover and maintains intracellular homeostasis. However, the balance is often dysregulated in many cancers, including HCC. Autophagy and apoptosis pathways may be either independent or parallel or one may influence the other. Autophagy may either inhibit or promote apoptosis, thus regulating the fate of the liver cancer cells. In this review, a concise overview of the pathogenesis of HCC is presented, with emphasis on new developments, including the role of endoplasmic reticulum stress, the implication of microRNAs and the role of gut microbiota. The characteristics of HCC associated with a specific liver disease are also described and a brief description of autophagy and apoptosis is provided. The role of autophagy and apoptosis in the initiation, progress and metastatic potential is reviewed and the experimental evidence indicating an interplay between the two is extensively analyzed. The role of ferroptosis, a recently described specific pathway of regulated cell death, is presented. Finally, the potential therapeutic implications of autophagy and apoptosis in drug resistance are examined.

The Interplay between Medical Plants and Gut Microbiota in Cancer

“…In fact, an important interindividual variability has been observed in glucoraphanin pharmacokinetics and it could reflect the different composition of enteric microbiota influencing polymorphisms in genes involved in dithiocarbamate production and the amount of glucoraphanin hydrolysis. Nonetheless, this evidence opens the road to a possible rational and practical use of food-derived molecules as chemopreventive agents [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99].…”

Noncoding RNAs and programmed cell death in hepatocellular carcinoma: Significant role of epigenetic modifications in prognosis, chemoresistance, and tumor recurrence rate

“…The pathogenic events of HCC are described as a complex and multifactorial occurrence that has not been uncovered yet; however, the role of some cellular and molecular mechanisms has been determined (Polyzos et al, 2023). Preclinical documents implicated that the origin of HCC cells is possibly transformed hepatocytes or liver stem cells (Kouroumalis et al, 2023). Some mutations, such as mutations in the p53 suppressor gene and TERT promoter, can have a causative role in HCC pathogenesis.…”

“…Coding genes for different signaling pathways, for instance, MAPK, Akt/mammalian target of rapamycin, Wnt/β-catenin, and oxidative stress-related pathways, are mostly mutated in HCC. These molecular changes occur by external agents, like unhealthy nutrition, viral infection, and alcohol taking (Kouroumalis et al, 2023). In addition to the mentioned causes, cell cycle defect, aberrant DNA methylation, microRNA (miRNA) impairment, immune regulation disruption, oxidative stress, and epithelial-to-mesenchymal cell transformation (EMT) (Zhao et al, 2023).…”

Hepatocellular Carcinoma Prevention in the Era of Hepatitis C Elimination

“…Another cytoplasmic event that may contribute to HCC onset is steatosis, i.e., the accumulation of triglycerides in hepatocytes due to HCV’s core ability to reduce triglyceride transfer protein activity and cause oxidative stress that contributes to the oncogenic process [ 31 ]. The altered composition of the gut microbiota has been involved in HCV-related HCC following studies with whole-genome sequencing of fecal DNA from patients with HCV-related HCC and the demonstration that the transplantation of microbiota from patients with HCC into mice amplified liver cancer incidence as compared with mice with transplanted microbiota from healthy donors [ 32 ].…”