Kouroumalis Elias, Tsomidis Ioannis, Voumvouraki Argyro
Department of Gastroenterology, PAGNI University Hospital, University of Crete School of Medicine, 71500 Heraklion, Crete, Greece.
Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece.
Biomedicines. 2023 Apr 13;11(4):1166. doi: 10.3390/biomedicines11041166.
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.
肝细胞癌（HCC）的发病机制是一个多因素过程，尚未得到充分研究。自噬和凋亡是两个重要的细胞途径，对细胞存活或死亡至关重要。凋亡和自噬之间的平衡调节肝细胞更新并维持细胞内稳态。然而，在包括HCC在内的许多癌症中，这种平衡常常失调。自噬和凋亡途径可能是独立的、平行的，也可能相互影响。自噬可能抑制或促进凋亡，从而调节肝癌细胞的命运。在这篇综述中，简要概述了HCC的发病机制，重点介绍了新进展，包括内质网应激的作用、微小RNA的影响以及肠道微生物群的作用。还描述了与特定肝脏疾病相关的HCC的特征，并提供了自噬和凋亡的简要描述。综述了自噬和凋亡在起始、进展和转移潜能中的作用，并广泛分析了表明两者之间相互作用的实验证据。介绍了铁死亡（一种最近描述的受调控细胞死亡的特定途径）的作用。最后，研究了自噬和凋亡在耐药性方面的潜在治疗意义。
