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Extensively published in over 140 peer reviewed articles and book chapters, his research interests focus on the metabolic processes of cancer cells, including how glucose metabolism affects tumor growth and how these studies may lead to new developments in targeted cancer therapy. All rights reserved. Gonzlez, A., Hall, M. N., Lin, S. C. & Hardie, D. G. AMPK and TOR: the yin and yang of cellular nutrient sensing and growth control. Liu GJ. TME is composed of extracellular matrix, tumor-associated fibroblasts, endothelial cells, epithelial cells, and immune cells, which are essential in the occurrence, development, invasion, metastasis, and treatment of EC [37]. Fan, J. et al. Christen, S. et al. We have identified crucial metabolic differences between cisplatin-. Animal experiments were performed in accordance with protocols approved by the Animal Care and Use Committee of Tongji Medical College. Lacroix, M., Riscal, R., Arena, G., Linares, L. K. & Le Cam, L. 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Biology and Biochemistry, Copyright 2023 Research.com. 7a-b). Basic Journal Info Journal ISSN: 20493002 Publisher: NA History: NA Journal Hompage: Link How to Get Published: Find out more Research Categories Scope/Description: NA -------------------------------- 8d). Oncogene. 2023;51(D1):D58792. Metab. Cell Biol. Proc. 1a), the survival status (Supplement Fig. Cell 169, 258272.e17 (2017). Amino acid metabolism has extremely extensive effects in cancer cells, including, but not limited to, (1) establishing amino acid pools as building blocks, especially the production of non-essential amino acids for protein biosynthesis, conversion to glucose, lipids, and precursors of nitrogen-containing metabolites, such as purines and pyrimidi. Chi Dang is a professor, physician-researcher, renowned cancer biologist and hematologist-oncologist, who serves as director of the Abramson Cancer Center at the University of Pennsylvania. Fatty acid synthesis is required for breast cancer brain metastasis. Sulkowski, P. L. et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. The shRNA of TIMM50 was purchased from GenChem(Shanghai, China). ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis. 33, 211221.e6 (2021). Zhu, Z. et al. 82103157). Reinfeld, B. I. et al. Google Scholar. 5e). PubMed 2021;256:43365. Invest. 3f). Ubellacker, J. M. et al. Jacobs, S. R. et al. Bosc, C. et al. Cell Metab. Oncometabolites suppress DNA repair by disrupting local chromatin signalling. The epigenetic modification of the oxytocin receptor (OTR) via DNA methylation stimulates parturition and breast milk secretion and inhibits craniopharyngioma, breast cancer, and ovarian cancer growth significantly as well as directly regulates bone metabolism in their peripheral form rather than the central form. Metabolic reprogramming in cancer primarily includes glycolysis, increased glutamine consumption, and increased fatty acid synthesis [6]. Krall, A. S. et al. Clarke MA. To explore the impact of LMRGS on EC progression, we elucidated the relationship between LMRGS and clinicopathological factors, including age, stage, pathological grade and risk score. Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth. Hangauer, M. J. et al. Maddocks, O. D. K. et al. Rev. JAMA Intern Med. Article 7c-d). Assay to visualize specific protein oxidation reveals spatio-temporal regulation of SHP2. Rev. The KEGG database has been developed as a computer model of biological information systems represented in terms of molecular interaction and reaction networks [28]. A renowned innovative researcher in his field, Dr. Vander Heiden received the 2017 Philip A. a Images of subcutaneous injection of BALB/c nude mice. + expression level of genen coefficient of genen [23]. Animal experiments were carried out in accordance with relevant guidelines and regulations. The CC were mainly participated in the mitochondrial matrix, mitochondrial inner membrane, mitochondrial protein-containing complex, respiratory chain complex, NADH dehydrogenase complex, etc. ", Dr. Matthew G. Vander Heiden, co-Editor-in-Chief. Remarkably, the predictive capability of these traditional clinical parameters (age, grade, and stage) was significantly lower than that of the LMGRs risk score. If material is not included in the articles Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. 21, 183203 (2020). Biancur, D. E. et al. Privacy By searching with the keywords lactate the Molecular Signatures database v7.4 (MSigDB; https://www.gsea-msigdb.org/gsea/msigdb) [19], and 5 lactate-related pathways (GOBP_LACTATE_METABOLIC_PROCESSHP_INCREASED_SERUM_LACTATEHP_LACTIC_ACIDOSISHP_LACTICACIDURIAHP_SEVERE_LACTIC_ACIDOSIS) were obtained, and 289 lactate metabolism-related genes were integrated by eliminating the duplicated genes. In contrast, lactate facilitates the maintenance of immunosuppressive functions of FOXP3+ regulatory T (Treg) cells in an acidic environment. Dey P, Kimmelman AC, DePinho RA. 6, eabb7272 (2020). Shim, H. et al. Cardaci, S. et al. Edu assay was performed using Edu kit (#C0071S, Beyotime, shanghai), according to the instructions. Condon, K. J. et al. Nature 585, 288292 (2020). EC is one of the most common cancers among women, with 417,000 new diagnoses worldwide in 2020 [1]. Patients were categorized into two groups based on the optimal cutoff value for the risk of LMRGs for diagnostic accuracy (Fig. A metastasis map of human cancer cell lines. Metabolic heterogeneity in human lung tumors. J. Immunol. More mortality events were observed in the high-risk group, suggesting that the increased risk of LMRGs reflected an unfavorable prognosis for EC patients (Fig. Hui, S. et al. Xiao, H. et al. 8, 466 (2017). After 1.5h of skim milk closure and overnight incubation with primary antibody at 4C, the membranes were washed with TBST. Science 339, 16211625 (2013). Cell 78, 10191033 (2020). 3a). PubMed A mitochondrial switch promotes tumor metastasis. Ji LJ. The clinical features of EC usually present as post-menopausal bleeding, but only 510% of women with post-menopausal bleeding are associated with the potential for endometrial malignancy [3]. Nat. It is now becoming clear that these differences may be a driving force of cancer cells. A three-dimensional illustration of a cancer cell in the process of mitosis. Baking industry food additive raises red flag, expert says. 23, 13621368 (2017). & Commisso, C. Macropinocytosis in cancer: a complex signaling network. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Med. Transaminase inhibition by 2-hydroxyglutarate impairs glutamate biosynthesis and redox homeostasis in glioma. Cancers (Basel). Frontiers in Oncology is delighted to present the 'Reviews in' series of article collections. To confirm the association between LMRGs and prognosis, univariate COX regression analysis was performed and 18 genes were identified to be associated with EC prognosis, including TP53, MRPL3, NDUFA11, NAXE, CYP27A1, PDSS1, RNASEH1, ACAT2, MECP2, NDUFB9, PDHA1, CARS2, HPDL, ATPAF2, TIMM50, FBP1, ALDOB, NDUFA6(Fig. PubMedGoogle Scholar. Cell Metab. These results demonstrate the unique characteristics of the EC immune microenvironment and provide a useful addition to basic research. c GO enrichment analysis. Total Citations in 2020 and 2021 = 500. Article Google Scholar. Mol. (R)-2-Hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Autophagy promotes growth of tumors with high mutational burden by inhibiting a T-cell immune response. 4b). A growing number of studies suggest that proton-coupled lactate efflux from cancer cells or stromal cells plays a critical role in maintaining an acidic phenotype and increasing tumor progression by regulating TME, including cell invasion, angiogenesis, survival signaling, metastasis development, and escape from immunosurveillance [16]. Cancer Metab. Liberzon A. et.al, Molecular signatures database (MSigDB) 3.0. Navdeep S. Chandel Nature Reviews Cancer 21 , 669-680 ( 2021) Cite this article 38k Accesses 328 Citations 202 Altmetric Metrics Abstract Tumour initiation and progression requires the metabolic. Obesity and exercise are associated with better and worse outcomes, respectively, and. POLE mutation/high mutation and microsatellite instability (MSI)) are highly immunogenic and exhibit more tumor-specific neoantigens, leading to increased CD3+ and CD8+ tumor-infiltrating lymphocytes and compensatory upregulation of immune checkpoints [38]. PubMed Central The results indicated that TP53 was the most mutated gene (Fig. Knockdown of TIMM50 suppressed EC cell proliferation, migration, and lactate synthesis. Associate Editors: Kivanc Birsoy,The Rockefeller University, USAKevin Brindle,University of Cambridge, UKNavdeep Chandel,Northwestern University, USAMaralice Conacci Sorrell,University of Texas Southwestern Medical Center,USALydia Finley, Memorial Sloan Kettering Cancer Center, USAChristian Frezza, University Hospital Cologne, GermanyRichard G. Kibbey,Yale University School of Medicine, USAMioara Larion, National Cancer Institute, Center for Cancer Research, National Institutes of Health, USAJason Locasale, Duke University School of Medicine, USACostas Lyssiotis,University of Michigan, USAChristian Metallo,Salk Institute for Biological Studies, USARachel Perry,Yale University School of Medicine, USAJulie St-Pierre,University of Ottawa, Canada, Editorial Board Members:Abass Alavi,University of Pennsylvania School of Medicine, USALewis Cantley,Weill Cornell Medical College, USAPeter Carmeliet,Vesalius Research Center, BelgiumGina DeNicola,Moffitt Cancer Center, USARobert Gatenby,Moffitt Cancer Center, USAKun-Liang Guan,University ofCalifornia,USA, Andrew Lane,Markey Cancer Center, USASophia Lunt, Michigan State University, USAChristian Metallo, University of California, San Diego Department of Bioengineering, USAGordon Mills, University of Texas M. D. Anderson Cancer Center, USAMichael E Pacold, New York University Langone Health, USAThales Pappagiannokopoulos, NYU Grossman School of Medicine, USAJacques Pouyssegur,Institute of Research on Cancer and Aging, FranceJoshua Rabinowitz,Princeton University, USAPeter Ratcliffe,Nuffield Department of Clinical Medicine, UKJeffrey Rathmell, Duke University, USAJared Rutter,University of Utah School of Medicine, USAGregg Semenza,Johns Hopkins University School of Medicine, USACeleste Simon,University of Pennsylvania School of Medicine, USABert Vogelstein,Johns Hopkins University School of Medicine, USAKaren Vousden,Beatson Institute for Cancer Research, UKEileen White,The Cancer Institute of New Jersey, USA. 2d). Lactate metabolism-related genes to predict the clinical outcome and molecular characteristics of endometrial cancer. Antioxidants accelerate lung cancer progression in mice. The authors contributed equally to all aspects of the article. Med. Mol. Et. Nature 560, 499503 (2018). 5% acetic acid differentiation for 1min, rinse with running water, add acetic acid by pipette drops, cloth can be covered with the tissue on the slide, the color became lighter and blue after differentiation. Med. J. Mol. EMBO J. Li, T. et al. Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. 15, 157170 (2012). 89, 213220 (2011). In vivo evidence for serine biosynthesis-defined sensitivity of lung metastasis, but not of primary breast tumors, to mTORC1 inhibition. Drug Discov. Bergers, G. & Fendt, S. M. The metabolism of cancer cells during metastasis. & Chandel, N. S. We need to talk about the Warburg effect. Functional genomics identifies metabolic vulnerabilities in pancreatic cancer. Annu. Quantitative analysis was performed using appropriate statistical methods. However, the lactic acid in EC is not fully understood. Interestingly, the predicted risk was similar to the actual risk, indicating the reliability of our nomogram (Fig. Harris, I. S. et al. An image of a cartoon face that is very unhappy. Metabolic reprogramming is one of hallmarks of cancer progression and is of great importance for the tumor microenvironment (TME). Deng HJ. Nature 577, 115120 (2020). The relative protein levels of TIMM50 were determined in subcutaneous xenograft tumours by IHC. 4g-h). Lactate also regulates the metabolism of innate and adaptive immune cells by inhibiting the function of CD8+ T cells, natural killer (NK) cells, natural killer T (NKT) cells and dendritic cells.