The Translational Bridge between Inflammation and Hepatocarcinogenesis

Gufler, Sabine; Seeboeck, Rita; Schatz, Christoph; Haybaeck, Johannes

doi:10.3390/cells11030533

Cited by 11 publications

(5 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mTOR is a critical regulatory factor for environmental and hormonal signals . Adequate nutrition can regulate mTOR to activate anabolic metabolic processes and inhibit catabolic metabolic processes . Recent studies have shown that cholesterol, a fundamental building block of cell growth, is identified as a critical regulator of mTOR activation, which can promote mTOR recruitment to the lysosomal membrane, thus initiating downstream processes, improving anabolism, inhibiting catabolism and ultimately affecting nutrient uptake .…”

Section: Discussionmentioning

confidence: 99%

Stigmasterol Activates the mTOR Signaling Pathway by Inhibiting ORP5 Ubiquitination to Promote Milk Synthesis in Bovine Mammary Epithelial Cells

Sun,

Cao,

Cheng

et al. 2024

J. Agric. Food Chem.

View full text Add to dashboard Cite

Stigmasterol (ST), a phytosterol found in food, has various biological activities. However, the effect of ST on milk synthesis in dairy cows remains unclear. Therefore, bovine primary mammary epithelial cells (BMECs) were isolated, cultured, and treated with ST to determine the effect of ST on milk synthesis. The study revealed that 10 μM ST significantly increased milk synthesis in BMECs by activating the mammalian target of rapamycin (mTOR) signaling pathway. Further investigation revealed that this activation depends on the regulatory role of oxysterol binding protein 5 (ORP5). ST induces the translocation of ORP5 from the cytoplasm to the lysosome, interacts with the mTOR, recruits mTOR to target the lysosomal surface, and promotes the activation of the mTOR signaling pathway. Moreover, ST was found to increase ORP5 protein levels by inhibiting its degradation via the ubiquitin-proteasome pathway. Specifically, the E3 ubiquitin ligase membrane-associated cycle-CH-type finger 4 (MARCH4) promotes the ubiquitination and subsequent degradation of ORP5. ST mitigates the interaction between MARCH4 and ORP5, thereby enhancing the structural stability of ORP5 and reducing its ubiquitination. In summary, ST stabilizes ORP5 by inhibiting the interaction between MARCH4 and ORP5, thereby activating mTOR signaling pathway and enhancing milk synthesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Stigmasterol Activates the mTOR Signaling Pathway by Inhibiting ORP5 Ubiquitination to Promote Milk Synthesis in Bovine Mammary Epithelial Cells

Sun,

Cao,

Cheng

et al. 2024

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

“…CCL2, also referred to as monocyte chemoattractant protein 1 (MCP1), triggers chemotaxis, prompting monocytes derived from the peripheral blood or bone marrow to infiltrate into the liver and to differentiate into macrophages [69,70]. This pro-inflammatory environment is enhanced by the release of TNF-α and IL-6 locally in the liver, but is also caused by systemic chronic inflammation processes derived from metabolic tissues such as adipose tissue resulting from insulin resistance [71], and by high leptin but low adiponectin levels, which are typically found in people who are overweight [71,72]. In all, this triggering of the innate immune response marks the transition of simple steatosis to actual steatohepatitis [68,73] and plays a key part in the initiation of NAFLD-related HCC.…”

Section: Inflammatory Pathways In the Pathogenesis Of Nafld And Nafld...mentioning

confidence: 99%

Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease

Son

Verschuren

Hanemaaijer

et al. 2023

Cancers

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) in the setting of non-alcoholic fatty liver disease (NAFLD)-related cirrhosis and even in the pre-cirrhotic state is increasing in incidence. NAFLD-related HCC has a poor clinical outcome as it is often advanced at diagnosis due to late diagnosis and systemic treatment response is poor due to reduced immune surveillance. Much of the focus of molecular research has been on the pathological changes in hepatocytes; however, immune cells, hepatic stellate cells, liver sinusoidal endothelial cells and the extracellular matrix may play important roles in the pathogenesis of NAFLD-related HCC as well. Here, we review the role of non-parenchymal cells in the liver in the pathogenesis of HCC in the context of NAFLD-NASH, with a particular focus on the innate and the adaptive immune system, fibrogenesis and angiogenesis. We review the key roles of macrophages, hepatic stellate cells (HSCs), T cells, natural killer (NK) cells, NKT cells and liver sinusoidal endothelial cells (LSECs) and the role of the extracellular matrix in hepatocarcinogenesis within the steatotic milieu.

show abstract

“…NLRP3 activation in hepatic stellate cells (HSCs) promotes the production of the profibrogenic cytokine and induces the expression of the profibrogenic molecule TGF-β. These events in concert lead to liver inflammation and fibrosis, being the link between liver damage and hepatocellular carcinoma [ 38 , 39 ].…”

Section: Pathogenesis Of Hccmentioning

confidence: 99%

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

2023

View full text Add to dashboard Cite

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.

show abstract

The Translational Bridge between Inflammation and Hepatocarcinogenesis

Cited by 11 publications

References 124 publications

Stigmasterol Activates the mTOR Signaling Pathway by Inhibiting ORP5 Ubiquitination to Promote Milk Synthesis in Bovine Mammary Epithelial Cells

Stigmasterol Activates the mTOR Signaling Pathway by Inhibiting ORP5 Ubiquitination to Promote Milk Synthesis in Bovine Mammary Epithelial Cells

Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

Contact Info

Product

Resources

About