[Cholesterol Metabolism and Tumor Immunity].

Cholesterol, an important lipid molecule of organisms, is involved in the formation of cell membrane structure, bile acid metabolism and steroid hormone synthesis, playing an important role in the regulation of cell structure and functions. In recent years, a large number of studies have shown that cholesterol metabolism is reprogrammed during tumor formation and development. In addition to directly affecting the biological behavior of tumor cells, cholesterol metabolic reprogramming also regulates the antitumor activity of immune cells in the tumor microenvironment.

[Phosphorylation of eukaryotic initiation factor 2-alpha inhibits cisplatin-mediated apoptosis of hepatocellular carcinoma cells].

Objective: To investigate whether the phosphorylation (functionally inhibitive) of eukaryotic initiation factor 2-alpha (eIF2-a) affects the molecular mechanism of cisplatin-induced cellular apoptosis in human hepatocellular carcinoma (HCC).

Methods: The human HCC cultured cell lines SMMC-7221 and HepG2 were treated with cisplatin alone (controls; 24 h) or in combination with pre-transfection of a dominant-negative eIF2-a mutant (eIF2aS51A) or pre-exposure to an eIF2-a-specific phosphatase inhibitor (salubrinal) to decrease or increase the phosphorylation level, respectively. Changes in expression of apoptosis markers were quantitatively and qualitatively assessed by flow cytometry and western blot analysis.

The suppressive role of p38 MAPK in cellular vacuole formation.

Vacuolization of the cytoplasm is one of the dramatic and frequently observed phenomena in various cell types. Cellular vacuoles occur spontaneously or via a wide range of inductive stimuli, but the molecular mechanism involved in this process remains largely unknown. In this study, we investigated the role of the p38 and JNK pathways in the formation of cytoplasmic vacuoles.

c-Met function requires N-linked glycosylation modification of pro-Met.

c-Met, the receptor for hepatocyte growth factor (HGF), is cell surface tyrosine kinase that controls cancer cell growth, survival, invasion, and metastasis. Post-translational modification, such as glycosylation, plays an essential role in regulating the function of cell surface molecules. Whether glycosylation modification regulates the enzymatic properties of c-Met is unknown.

Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats.

Background & Aims: Due to its anatomic connection, the liver is constantly exposed to gut-derived bacterial products or metabolites. Disruption of gut homeostasis is associated with many human diseases. The aim of this study was to determine the role of gut homeostasis in initiation and progression of hepatocellular carcinoma (HCC).

High expression of proline-rich tyrosine kinase 2 is associated with poor survival of hepatocellular carcinoma via regulating phosphatidylinositol 3-kinase/AKT pathway.

Background: The peritumoral environment has been implicated to be important in the process of metastasis and recurrence in hepatocellular carcinoma (HCC). Our aims were to assess the prognostic value of proline-rich tyrosine kinase 2 (Pyk2) in HCC and investigate related molecular mechanism.

Methods: Expression of Pyk2 was tested by immunohistochemistry in tissue microarrays containing 141 paired HCC samples.

p28(GANK) prevents degradation of Oct4 and promotes expansion of tumor-initiating cells in hepatocarcinogenesis.

Background & Aims: Hepatocellular carcinoma (HCC) is believed to arise from tumor-initiating cells (T-ICs), although little is known about their stem cell-like properties.

Methods: We quantified levels of p28(GANK) (Gankyrin), OV6, and Oct4 in 130 human HCC samples using immunohistochemistry. Magnetic-activated cell sorting was used to isolate OV6+ HCC cells.

The oncoprotein p28GANK establishes a positive feedback loop in β-catenin signaling.

p28(GANK) (also known as PSMD10 or gankyrin) is a novel oncoprotein that is highly expressed in hepatocellular carcinoma (HCC). Through its interaction with various proteins, p28(GANK) mediates the degradation of the tumor suppressor proteins Rb and p53. Although p53 was reported to downregulate β-catenin, whether p28(GANK) is involved in the regulation of β-catenin remains uncertain.

[The role of mir-221/222 in inhibiting endoplasmic reticulum stress-induced human hepatocarcinoma cell apoptosis].

Objective: To investigate the role of miR-221/222 in inhibiting endoplasmic reticulum stress-induced human hepatocarcinoma cells apoptosis.

Method: miR-221/222 mimics and inhibitors were used to mimic or block the function of endogenous miR-221/222 respectively. Western blot and flow cytometry were used to test the effects of miR-221/222 on cell cycle and apoptosis under endoplasmic reticulum stress in human hepatocellular carcinoma cells.

[Cross-talk between PI3K/Akt and MEK/ERK pathways regulates human hepatocellular carcinoma cell cycle progression under endoplasmic reticulum stress].

Objective: To investigate the cross-talk between the PI3K/Akt and MEK/ERK pathways and its role in cell cycle regulation under endoplasmic reticulum stress in human hepatocellular carcinoma cells.

Methods: PI3K inhibitor LY294002 and MEK inhibitor U0126 were used to block the PI3K/Akt and MEK/ERK pathways respectively, and constitutively activated Akt mutant construct was used to activate the PI3K/Akt pathway. Western blot was used to study the potential cross-talk between the PI3K/Akt and MEK/ERK pathways under endoplasmic reticulum stress in human hepatocellular carcinoma cells.

p28GANK inhibits endoplasmic reticulum stress-induced cell death via enhancement of the endoplasmic reticulum adaptive capacity.

It has been shown that oncoprotein p28(GANK), which is consistently overexpressed in human hepatocellular carcinoma (HCC), plays a critical role in tumorigenesis of HCC. However, the underlying mechanism remains unclear. Here, we demonstrated that p28(GANK) inhibits apoptosis in HCC cells induced by the endoplasmic reticulum (ER) stress.