Stromal cell populations in the tumor microenvironment (TME) play a critical role in the oncogenesis and metastasis of renal cell carcinoma. In this study, we found that there are α-smooth muscle actin positive (α-SMA (+)) cells in the stroma of clear cell renal cell carcinoma (ccRCC) tissues, and their numbers are significantly associated with poor survival in ccRCC patients. Interleukin 6 (IL-6) is a critical diver that induces α-SMA (+) cells in ccRCC tissues via promotion of epithelial to mesenchymal transition (EMT) and stimulates migration and invasion in ccRCC. Peritumoral CD4+ T cells are the main source of IL-6 in ccRCC tissues. In addition to biochemical factors, mechanical compression within tumors affects tumor cell behavior. Tumors grown in a confined space exhibit intratumoral compressive stress and, with sufficient pressure, stress-stimulated migration of cancer cells. Moreover, a combination of IL-6 secreted by CD4+ T cells and growth-induced solid stress further contributes to the regulation of cancer cell morphogenesis, EMT and acquisition of a stemness phenotype. The effects in the combination group were driven by the Akt/GSK-3β/β-catenin signaling pathway, and deregulation of β-catenin expression was predictive of poor outcome in ccRCC patients. Notably, the expression of a cancer stem cell marker, CD44, was correlated with T stage, high Fuhrman grade and metastasis in ccRCC. These data provide evidence for new stress-reducing and IL-6 targeting strategies in cancer therapy.

As a potent neurotoxic agent, acrylamide (ACR) is formed in food processing at higher temperature. Taurine (TAU), a nonessential amino acid, is used to cure neurodegenerative disorders, followed by activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. In this article, we certified that antiapoptotic efficacy of TAU in vivo and vitro. ACR-treated rats received TAU by drinking water 2 weeks after ACR intoxication. The results showed that in treated rats, TAU alleviated ACR-induced neuronal apoptosis, which was associated with the activation of PI3K/AKT signaling pathway. TAU attenuated apoptosis caused by ACR through observing terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, measure of protein expression of Bcl-2, Bax, and caspase 3 activity. TAU-induced antiapoptotic effect is PI3K/AKT-dependent, which was proved in ACR-intoxicated ventral spinal cord 4.1 cells in the presence of AKT inhibitor, MK-2206. Therefore, our results demonstrated that TAU-attenuated ACR-induced apoptosis in vivo through a PI3K/AKT-dependent manner provided new sights in the molecular mechanism of TAU protection against ACR-induced neurotoxicity.