Abstract：
The tumor microenvironment (TME) consists of tumor cells, non-tumor cells, extracellular matrix, and signaling molecules, which can contribute to tumor initiation, progression, and therapy resistance. In response to starvation, hypoxia, and drug treatments, tumor cells undergo a variety of deleterious endogenous stresses, such as hypoxia, DNA damage, and oxidative stress. In this context, to survive the difficult situation, tumor cells evolve multiple conserved adaptive responses, including metabolic reprogramming, DNA damage checkpoints, homologous recombination, up-regulated antioxidant pathways, and activated unfolded protein responses. In the last decades, the protein O-GlcNAcylation has emerged as a crucial causative link between glucose metabolism and tumor progression. Here, we discuss the relevant pathways that regulate the above responses. These pathways are adaptive adjustments induced by endogenous stresses in cells. In addition, we systematically discuss the role of O-GlcNAcylation-regulated stress-induced adaptive response pathways (SARPs) in TME remodeling, tumor progression, and treatment resistance. We also emphasize targeting O-GlcNAcylation through compounds that modulate OGT or OGA activity to inhibit tumor progression. It seems that targeting O-GlcNAcylated proteins to intervene in TME may be a novel approach to improve tumor prognosis.
摘要：
肿瘤微环境（TME）由肿瘤细胞组成，非肿瘤细胞,细胞外基质，和信号分子，这可能导致肿瘤的发生，programming,和治疗抵抗。为了应对饥饿，缺氧,和药物治疗，肿瘤细胞经历各种有害的内源性应激，如缺氧，DNA损伤,和氧化应激。在这种情况下，为了在困难的情况下生存，肿瘤细胞进化出多种保守的适应性反应，包括代谢重编程，DNA损伤检查站,同源重组，上调的抗氧化剂途径，并激活未折叠的蛋白质反应。在过去的几十年里，蛋白质O-GlcNAcylation已成为葡萄糖代谢与肿瘤进展之间的关键因果关系。这里,我们讨论了调节上述反应的相关途径。这些途径是细胞中内源性应激诱导的适应性调节。此外,我们系统地讨论了O-GlcNAcylation调节的应激诱导的适应性反应途径（SARPs）在TME重塑中的作用，肿瘤进展，和治疗阻力。我们还强调通过调节OGT或OGA活性以抑制肿瘤进展的化合物靶向O-GlcNAcylation。看来，靶向O-GlcNAcylated蛋白干预TME可能是改善肿瘤预后的新方法。
