STAT proteins in cancer: orchestration of metabolism

Li, Yijia; Martincuks, Antons; Herrmann, Andreas; Yu, Hua

doi:10.1038/s41568-022-00537-3

Cited by 118 publications

(63 citation statements)

References 270 publications

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“…Therefore, the metabolism of colon cancer cells is a key link that we have to pay attention to for the occurrence and development of tumors (32). It has been found that STAT proteins, as signal converters and transcriptional activators, affect tumor progression and drug resistance by regulating the dynamic metabolism of cancer cells, immune cells, and adipocytes, providing new targets for the treatment of metabolic reprogramming of cancer (33). The ADH family, ALDH family, GSTA family, GSR and HPGDS proteins were found to play critical roles in the metabolic pathways by proteinprotein interaction network and correlation analysis.…”

Section: Discussionmentioning

confidence: 99%

Glutathione Reductase change the tumor immune microenvironment and prognosis of colon cancer：A study based on proteomic analysis

Wang¹,

Ju²,

Chen³

et al. 2023

Preprint

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Background Colonic malignant tumor cells can cause metabolic changes in the harsh microenvironment. Glutathione reductase (GSR) plays a key role in anti-oxidative stress in tumor cells, but its specific mechanism remains unclear. Therefore, the objective of this study was to investigate the prognostic value of GSR in patients with colon cancer and its effect on tumor microenvironment. Methods Differential proteins of colon cancer and normal intestinal tissues were obtained by proteomic differential analysis, and key proteins in metabolic pathways were identified by enrichment analysis and protein-protein interaction network (PPI) analysis. Survival analysis, immune infiltration analysis and clinical information correlation analysis were performed. Results A total of 1209 differentially expressed proteins were identified in 10 colon cancer samples. GO and KEGG enrichment analysis showed that differential proteins were significantly enriched in metabolic pathways, with 144 enriched genes (p < 0.05). PPI analysis showed that ADH1A, ADH1B, ADH1C, ADH5, ALDH18A1, ALDH3A1, GSTA1, GSTA2, HPGDS and GSR were the key proteins in the differential proteins metabolic pathway of colon cancer. GEPIA2 survival analysis showed that GSR significantly affected overall survival of colon cancer patients (p = 0.0017, HR = 0.45). Timer and TISIDB database analysis showed that the expression of GSR in colon cancer can significantly affect the level of immune cell infiltration. UALCAN database analysis showed that GSR expression predicted better N stage, overall stage and lower TP53 mutation rate of colon cancer (p < 0.05). The results of HPA database analysis suggested that GSR was mainly expressed in the cytoplasm and nuclear membrane of colonic malignant tumor cells. Conclusions Our study found that GSR plays an important role in the metabolic pathway of colon cancer and affects the prognosis of patients with statistical significance. GSR significantly affects the tumor immune microenvironment, clinical stage and TP53 mutation rate of colonic malignancies. This study provides some basis for the mechanism research and treatment of colon malignancy.

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Section: Discussionmentioning

confidence: 99%

Glutathione Reductase change the tumor immune microenvironment and prognosis of colon cancer：A study based on proteomic analysis

Wang¹,

Ju²,

Chen³

et al. 2023

Preprint

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“…Signal transducer and activator of transcription (STAT) is a unique family of proteins that can bind to DNA 316 . The STAT family consists of STAT1, STAT2, STAT3, STAT4, STAT5, and STAT6 317,318 .…”

Section: Crbn Ligands and Their Utilizations In Protacsmentioning

confidence: 99%

PROTACs: A novel strategy for cancer drug discovery and development

Han

Sun

2023

MedComm

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Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: a small molecule that binds to a target protein, an E3 ligase ligand (consisting of an E3 ligase and its small molecule recruiter), and a chemical linker that hooks first two components together. In the past 20 years, we have witnessed advancement of multiple PRO-TAC degraders into the clinical trials for anticancer therapies. However, one of the major challenges of PROTAC technology is that only very limited number of E3 ligase recruiters are currently available as E3 ligand for targeted protein degradation (TPD), although human genome encodes more than 600 E3 ligases. Thus, there is an urgent need to identify additional effective E3 ligase recruiters for TPD applications. In this review, we summarized the existing RING-type E3 ubiquitin ligase and their small molecule recruiters that act as effective E3 ligands of PRO-TAC degraders and their application in anticancer drug discovery. We believe that this review could serve as a reference in future development of efficient E3 ligands of PROTAC technology for cancer drug discovery and development.

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“…STAT3 is a cytosolic transcription factor, which may interact with STAT family proteins and different signaling proteins. The resulting complexes affect cellular metabolism and immune response, and promote cancer cell proliferation and differentiation (1)(2)(3). STAT3 participates in cancer promotion, chemoresistance and also enhances neurodegeneration (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

“…The resulting complexes affect cellular metabolism and immune response, and promote cancer cell proliferation and differentiation (1)(2)(3). STAT3 participates in cancer promotion, chemoresistance and also enhances neurodegeneration (1)(2)(3). When STAT3 dimerizes upon stimulating with receptor associated kinases, the dimerized STAT3 becomes phosphorylated and migrates into nucleus to activate the transcription of cytokine-responsive genes (1-3).…”

Section: Introductionmentioning

confidence: 99%

“…When STAT3 dimerizes upon stimulating with receptor associated kinases, the dimerized STAT3 becomes phosphorylated and migrates into nucleus to activate the transcription of cytokine-responsive genes (1-3). STAT3 signaling regulates glycolysis, Warburg effect, oxidative phosphorylation, ROS production, lipid and glutamine metabolism in cancer cells, immune cells and adipocytes in the tumour microenvironment, and those changes can lead to altered antitumour immune responses in tumor microenvironment (3). STAT family proteins act similarly in response to cytokines and growth factors such as IFNs, EGF, IL5, IL6, HGF, LIF and BMP2.…”

Section: Introductionmentioning

confidence: 99%

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