The physiological role of autophagy in metabolism of the body involves both protein synthesis and degradation. The autophagy-lysosome and the ubiquitin-proteasome systems are the two major intracellular proteolytic mechanisms. Autophagy in hepatocytes is known to be quite active and contribute to its normal functions and the pathogenesis of liver diseases. The role of autophagy in liver diseases has been widely studied, and growing evidence has now shown that autophagy is involved in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC). However, the role of autophagy in the progression of liver fibrosis and prognosis of human HCC is not well known. Recent studies have demonstrated that tissue factor (TF) combined with coagulation factor VII (FVII) has a pathological role by activating a protease-activated receptor 2 (PAR2) for tumor growth. Autophagy-related LC3A/B-II formation induced by the inhibition of TF/FVII/PAR2 coagulation axis, particularly by FVII knockdown, was selectively mediated by the Atg7 induction. These results are consistent with clinical observations that indicate the important role of FVII activation in regulating autophagy in HCC. In this chapter, we discuss our findings in which FVII promotes growth and progression in HCC through ERK-TSC/mTOR signaling to repress autophagy and may play a pivotal role in conferring cirrhosis and other liver diseases.
Part of the book: Autophagy in Current Trends in Cellular Physiology and Pathology
Hepatocellular carcinoma (HCC) is a major worldwide health problem, which is expected to increase steadily due to different underlying liver diseases. Surgical treatment modalities including liver transplantation (LT) or liver resection (LR) are the mainstay options for early cases of HCC. Liver transplantation for well‐selected cases provides excellent survival outcomes comparable to nonmalignant indications of LT. Living donor liver transplantation (LDLT) is an alternative option or even the sole one in the current era of organ shortage problem and in some Asian countries where deceased organ donation is markedly reduced due to various reasons. The adoption of LDLT for HCC treatment elicited many dynamic changes and debates to the dilemma of LT as a whole. In this chapter, we focus on different perspectives of LDLT for HCC, including selection criteria evolution, controversial topics, ethical considerations, operative highlights, and other points.
Part of the book: Updates in Liver Cancer