Journal of cancer biology最新文献

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Proton Sensing GPCR's: The missing link to Warburg's Oncogenic Legacy? 质子传感GPCR：华宝致癌遗产的缺失环节？

Journal of cancer biology Pub Date : 2024-01-01 DOI: 10.46439/cancerbiology.5.066

Jessica Cornell, Samantha Rea, Leif R Neitzel, Charles H Williams, Charles C Hong

{"title":"Proton Sensing GPCR's: The missing link to Warburg's Oncogenic Legacy?","authors":"Jessica Cornell, Samantha Rea, Leif R Neitzel, Charles H Williams, Charles C Hong","doi":"10.46439/cancerbiology.5.066","DOIUrl":"10.46439/cancerbiology.5.066","url":null,"abstract":"A century after Otto Warburg's seminal discovery of aerobic glycolysis in cancer cells, a phenomenon dubbed the \"Warburg effect\", the mechanistic links between this metabolic rewiring and tumorigenesis remain elusive. Warburg postulated that this enhanced glucose fermentation to lactate, even in the presence of oxygen, stemmed from an \"irreversible respiratory injury\" intrinsic to cancer cells. While oxidative phosphorylation yields higher ATP, the Warburg effect paradoxically persists, suggesting that the excess lactate and acid production are worth the deficit. Since Warburg's discovery, it has been demonstrated that the acidic tumor microenvironment activates a myriad of pro-oncogenic phenotypes ranging from therapeutic resistance to immune escape. Here we propose that proton-sensing G-protein-coupled receptors (GPCRs) act as crucial heirs to Warburg's findings by transducing the acid signal from elevated glycolytic lactate into pro-oncogenic signals. The increased lactate production characteristic of the Warburg effect causes extracellular acidification. This acidic tumor microenvironment can activate proton-sensing GPCRs like GPR68, a proton-sensing receptor shown to stimulate proliferation, migration, and survival pathways in cancer cells. Such pH sensing is accomplished through protonation of key residues such as histidine, which causes a conformational change to activate various downstream signaling cascades including the MAPK, PI3K/Akt, Rho, and β-arrestin pathways implicated in tumor progression and therapeutic resistance. By coupling Warburg's \"respiratory injury\" to potent mitogenic signaling, proton-sensing GPCRs like GPR68 may unveil a longstanding mystery - why forgo efficient ATP generation? As heirs to Warburg's iconic metabolic observations, these proton sensors could represent novel therapeutic targets to disrupt the synergy between the Warburg effect and oncogenic signaling.","PeriodicalId":519926,"journal":{"name":"Journal of cancer biology","volume":"5 2","pages":"65-75"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The many faceted role of glycogen synthase kinase-3 (GSK-3) in T cells and cancer immunotherapy. 糖原合酶激酶-3（GSK-3）在 T 细胞和癌症免疫疗法中的多面作用。

Journal of cancer biology Pub Date : 2024-01-01 DOI: 10.46439/cancerbiology.5.058

Aurora Rivas Crespo, Silvia Guil Luna, Bastien Moës, Antonio Rodriguez, Christopher E Rudd

引用次数: 0

Targeting the PRMT1-cGAS-STING signaling pathway to enhance the anti-tumor therapeutic efficacy. 靶向PRMT1-cGAS-STING信号通路，提高抗肿瘤治疗效果。

Journal of cancer biology Pub Date : 2024-01-01 DOI: 10.46439/cancerbiology.5.064

Daoyuan Huang, Abdol-Hossein Rezaeian, Jingchao Wang, Yihang Qi, Hong Chen, Hiroyuki Inuzuka, Wenyi Wei

{"title":"Targeting the PRMT1-cGAS-STING signaling pathway to enhance the anti-tumor therapeutic efficacy.","authors":"Daoyuan Huang, Abdol-Hossein Rezaeian, Jingchao Wang, Yihang Qi, Hong Chen, Hiroyuki Inuzuka, Wenyi Wei","doi":"10.46439/cancerbiology.5.064","DOIUrl":"10.46439/cancerbiology.5.064","url":null,"abstract":"Activating innate immune signaling in tumor cells to enhance anti-tumor immunity and increase T cell-mediated killing is the core objective of tumor immunotherapy. PRMT1, one of the most crucial PRMTs, plays a critical role in tumor progression and innate immunity. Recent research revealed that PRMT1 can inhibit the enzymatic activity of cGAS in part through PRMT1-mediated Arg methylation, thereby suppressing the anti-tumor immune response of cells. As such, inhibiting or knocking down PRMT1 can synergistically enhance the efficacy of anti-PD-1 immunotherapy by activating the cGAS-STING signaling pathway. Here, we provide a comprehensive description of the two key signaling components, PRMT1 and cGAS, in the PRMT1-cGAS-STING signaling pathway for therapeutic intervention to augment anti-tumor immunity. By understanding the specific physiological functions and regulatory mechanisms of PRMT1, as well as the extensive post-translational modifications (PTMs) of cGAS, we have identified several compounds and drugs that can directly target PRMT1 or cGAS, and/or indirectly target PRMT1 upstream regulators or cGAS-post-translational modifying enzymes as potential means to activate the cGAS-STING signaling pathway. However, further investigation is needed on the efficacy of combining this pathway activation with anti-PD1 therapy. This review suggests that targeting the PRMT1-cGAS-STING pathway with immune checkpoint inhibitors is likely a promising approach in tumor immunotherapy.","PeriodicalId":519926,"journal":{"name":"Journal of cancer biology","volume":"5 2","pages":"44-60"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0