Relationship of mTORC1 and ferroptosis in tumors.

Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

The role of TGF-ß in the tumor microenvironment of pancreatic cancer.

Pancreatic cancer (PC) is an aggressive malignant tumor with low rate of surgical resection and poor prognosis. Transforming growth factor-ß (TGF-ß) is a cytokine that has both protumor and antitumor activities, depending on tumor microenvironment. The interaction between TGF-ß signaling and the tumor microenvironment in PC is complex. Here, we reviewed the role of TGF-ß in the tumor microenvironment of PC, highlighting producers of TGF-ß and TGF-ß responders in the tumor microenvironment of PC.

Cysteine Metabolism in Tumor Redox Homeostasis.

Cysteine (Cys) is a semi-essential nutrient amino acid that plays an important role in cells through endogenous production and various transport systems. Intracellular Cys can be used as a precursor of protein synthesis to maintain cell homeostasis and to generate sulfur-containing substances, including glutathione (GSH), hydrogen sulfide (H2S), and taurine. There have been quite a few reports that Cys is related to tumor occurrence and development, and its level is closely related to tumor proliferation, invasion, and metastasis. Moreover, it helps in maintaining the tumor redox balance and increasing drug resistance. This review aims to summarize the production and metabolism of Cys and its role in tumors, with special emphasis on the potential therapeutic value of Cys in tumors to improve the quality of life of cancer patients.

Feedback regulation of coronary artery disease susceptibility gene ADTRP and LDL receptors LDLR/CD36/LOX-1 in endothelia cell functions involved in atherosclerosis.

A high level of low-density lipoprotein cholesterol (LDL) is one of the most important risk factors for coronary artery disease (CAD), the leading cause of death worldwide. However, a low concentration of LDL may be protective. Genome-wide association studies revealed that variation in ADTRP gene increased the risk of CAD. In this study, we found that a low concentration of oxidized-LDL induced the expression of ADTRP. Further analyses showed that knockdown of the expression of LDL receptor genes LDLR, CD36, or LOX-1 significantly downregulated ADTRP expression, whereas overexpression of LDLR/CD36/LOX-1 markedly increased ADTRP expression through the NF-κB pathway. Like ADTRP, LDLR, CD36 and LOX-1 were all involved in endothelial cell (EC) functions relevant to the initiation of atherosclerosis. Downregulation of LDLR/CD36/LOX-1 promoted monocyte adhesion to ECs and transendothelial migration of monocytes by increasing expression of ICAM-1, VCAM-1, E-selectin and P-selectin, decreased EC proliferation and migration, and increased EC apoptosis, thereby promoting the initiation of atherosclerosis. Opposite effects were observed with the overexpression of ADTRP and LDLR/CD36/LOX-1 in ECs. Interestingly, through the NF-κB and AKT pathways, overexpression of ADTRP significantly upregulated the expression of LDLR, CD36, and LOX-1, and knockdown of ADTRP expression significantly downregulated the expression of LDLR, CD36, and LOX-1. These data suggest that ADTRP and LDL receptors LDLR/CD36/LOX-1 positively regulate each other, and form a positive regulatory loop that regulates endothelial cell functions, thereby providing a potential protective mechanism against atherosclerosis. Our findings provide a new molecular mechanism by which deregulation of ADTRP and LDLR/CD36/LOX-1 promote the development of atherosclerosis and CAD.