Wnt/ß­catenin signaling: Causes and treatment targets of drug resistance in colorectal cancer (Review).

Colorectal cancer (CRC) is the third most common malignant tumor in humans. Chemotherapy is used for the treatment of CRC. However, the effect of chemotherapy remains unsatisfactory due to drug resistance. Growing evidence has shown that the presence of highly metastatic tumor stem cells, regulation of non­coding RNAs and the tumor microenvironment contributes to drug resistance mechanisms in CRC. Wnt/ß­catenin signaling mediates the chemoresistance of CRC in these three aspects. Therefore, the present study analyzed the abundant evidence of the contribution of Wnt/ß­catenin signaling to the development of drug resistance in CRC and discussed its possible role in improving the chemosensitivity of CRC, which may provide guidelines for its clinical treatment.

Apatinib regulates the growth of gastric cancer cells by modulating apoptosis and autophagy.

Apatinib is a novel, highly selective small-molecule inhibitor of the tyrosine kinase VEGFR-2. Although its safety and efficacy in the treatment of advanced gastric cancer (GC) and other solid tumors have been confirmed, the precise molecular mechanism underlying its efficacy remains unclear. The purpose of this study was to investigate the mechanism by which apatinib regulates the biological functions of GC cells in vitro. The CCK-8 assay was used to detect the inhibitory effect of apatinib at different concentrations on the proliferation of SGC7901 and MKN45 human GC cells. The effects of apatinib on apoptosis, autophagy, and cell cycle-related genes in SGC7901 and MKN45 cells were detected by Western blotting and real-time quantitative PCR (RT-qPCR). JC-1 staining, flow cytometry, Hoechst 33342 staining, dansylcadaverine (MDC) staining, and Transwell assays were used to detect the effects of apatinib on apoptosis, the cell cycle, autophagy, and invasion and migration capacities, respectively, in SGC7901 and MKN45 cells. The inhibitory effect of apatinib on the proliferation of GC cells was dependent on concentration. Apatinib significantly promoted apoptosis and autophagy. It also altered the cell cycle distribution and inhibited the invasion and migration of GC cells. In general, apatinib inhibited the proliferation of GC cells by promoting apoptosis and autophagy, regulating the cell cycle and inhibiting the invasion and migration capacities of GC cells.

Role, function and regulation of the thymocyte selection-associated high mobility group box protein in CD8+ T cell exhaustion.

Thymocyte selection-associated high mobility group box protein (TOX), a member of the high-motility group box (HMG) protein superfamily, is an evolutionarily conserved DNA-binding protein. It functions as a transcription factor that modulates transcriptional programs by binding to DNA in a structure-dependent manner. It has been well established that TOX is required for the development of CD4+ T cells, natural killer (NK) cells and innate lymphoid cells (ILCs), as well as the autoimmunity mediated by CD8+ T cells. Recently, emerging evidence supports an essential role for TOX in the induction of T cell exhaustion in the setting of tumor or chronic viral infection by mediating transcriptional and epigenetic changes, which are cardinal hallmarks of exhausted T cells. Moreover, TOX plays a key role in the persistence of antigen-specific T cells and in the mitigation of tissue damage caused by immunopathology over the course of tumorigenesis and chronic infection. Additionally, TOX contributes to the high level of programmed cell death protein 1 (PD-1) on the cell surface by participating in the process of endocytic recycling of PD-1. In this review, we summarize the most recent information about the role of TOX in the process of T cell exhaustion, which enriches our understanding of the molecular mechanisms of CD8+ T cell exhaustion upon chronic antigen stimulation and reveals promising therapeutic targets for persisting infection and cancer.

Non­coding RNAs that regulate the Wnt/ß­catenin signaling pathway in gastric cancer: Good cop, bad cop? (Review).

Gastric cancer (GC) is one of the most common causes of cancer­related mortality worldwide. Despite remarkable progress in the diagnosis and treatment of GC, a large number of cases are diagnosed as advanced GC, and treatment failure occurs. Emerging evidence has shown that non­coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non­coding RNAs (lncRNAs), play a vital role in the tumorigenesis and development of GC. Moreover, the pathogenesis of GC is closely related to aberrant activation of the Wnt (Wingless­type MMTV integration site family) signaling pathway. ncRNAs serve as potential novel biomarkers in the clinical examination, prognosis and therapeutic targeting of GC. Furthermore, dysregulation of ncRNAs has been demonstrated to affect tumor initiation, epithelial­mesenchymal transition (EMT), angiogenesis, tumor development, invasion, metastasis and resistance to therapy via the Wnt/ß­catenin signaling pathway. This review focuses on the role of ncRNAs in modulating the Wnt/ß­catenin signaling pathway in the pathogenesis of GC, which may provide a reference for the clinical diagnosis and treatment of GC.