GLUT3 promotes macrophage signaling and function via RAS-mediated endocytosis in atopic dermatitis and wound healing DOI Creative Commons

Dong-Min Yu,

Jiawei Zhao,

Eunice E. Lee

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(21)

Published: Sept. 18, 2023

The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that expression increased after M1 polarization stimuli found M2 stimulation macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired bone marrow-derived Alternatively activated macrophages from the skin patients with atopic dermatitis showed expression, a calcipotriol-induced model was rescued LysM-Cre Glut3fl/fl mice. M2-like human wound tissues as assessed by transcriptomics costaining, significantly decreased nonhealing, compared healing, diabetic foot ulcers. In an excisional healing model, mice macrophage delayed healing. promoted IL-4/STAT6 signaling, independently its glucose transport activity. Unlike plasma membrane-localized GLUT1, localized primarily to endosomes required for efficient endocytosis IL-4Rα subunits. interacted directly GTP-bound RAS vitro vivo through intracytoplasmic loop domain, this interaction STAT6 activation polarization. PAK macropinocytosis were also without GLUT3, suggesting broader roles regulation endocytosis. Thus, is alternative function, transport-independent, RAS-mediated role activation.

Language: Английский

What is cancer metabolism? DOI Creative Commons
Lydia W.S. Finley

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1670 - 1688

Published: Feb. 28, 2023

Language: Английский

Citations

160
Tumor microenvironment signaling and therapeutics in cancer progression DOI Creative Commons
Anshika Goenka, Fatima Khan, Bhupender Verma

et al.

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(5), P. 525 - 561

Published: April 2, 2023

Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.

Language: Английский

Citations

124
Acetyl-CoA regulates lipid metabolism and histone acetylation modification in cancer DOI
Weijing He, Qingguo Li, Xinxiang Li

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2022, Volume and Issue: 1878(1), P. 188837 - 188837

Published: Nov. 17, 2022

Language: Английский

Citations

73
Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma DOI Creative Commons
Fei Li, Wenzhe Si, Li Xia

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 6, 2024

Abstract Background Metabolic reprogramming and epigenetic alterations contribute to the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). Lactate-dependent histone modification is a new type mark, which links glycolysis metabolite process lactylation. However, role lactylation in PDAC remains unclear. Methods The level was identified by western blot immunohistochemistry, its relationship with overall survival evaluated using Kaplan-Meier plot. participation growth progression confirmed through inhibition inhibitors or lactate dehydrogenase A ( LDHA ) knockdown both vitro vivo. potential writers erasers were functional experiments. target genes H3K18 (H3K18la) screened CUT&Tag RNA-seq analyses. candidate TTK protein kinase BUB1 mitotic checkpoint serine/threonine B BUB1B validated ChIP-qPCR, RT-qPCR Next, effects these two overexpression. interaction between Co-IP assay. Results Histone lactylation, especially H3K18la elevated PDAC, high associated poor prognosis. suppression glycolytic activity different kinds contributed anti-tumor E1A binding p300 (P300) deacetylase 2 writer eraser cells, respectively. enriched at promoters activated transcription regulators . Interestingly, could elevate expression P300 turn increased glycolysis. Moreover, phosphorylated tyrosine 239 (Y239) LDHA, subsequently upregulated levels. Conclusions glycolysis-H3K18la-TTK/BUB1B positive feedback loop exacerbates dysfunction PDAC. These findings delivered exploration significant inter-relationship metabolic regulation, might pave way toward novel treatment strategies therapy.

Language: Английский

Citations

58
Mendelian inheritance revisited: dominance and recessiveness in medical genetics DOI
Johannes Zschocke, Peter H. Byers, Andrew O.M. Wilkie

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(7), P. 442 - 463

Published: Feb. 20, 2023

Language: Английский

Citations

54
LDHA promotes osteoblast differentiation through histone lactylation DOI

Feige Nian,

Yezhou Qian,

Fangyan Xu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2022, Volume and Issue: 615, P. 31 - 35

Published: May 13, 2022

Language: Английский

Citations

53
Metabolic enzyme LDHA activates Rac1 GTPase as a noncanonical mechanism to promote cancer DOI

Juan Liu,

Cen Zhang, Tianliang Zhang

et al.

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(12), P. 1830 - 1846

Published: Dec. 19, 2022

Language: Английский

Citations

47
Metabolic and Nonmetabolic Functions of PSAT1 Coordinate Signaling Cascades to Confer EGFR Inhibitor Resistance and Drive Progression in Lung Adenocarcinoma DOI Open Access
Mingyu Luo, Ye Zhou,

Wei-ming Gu

et al.

Cancer Research, Journal Year: 2022, Volume and Issue: 82(19), P. 3516 - 3531

Published: Oct. 4, 2022

Emerging evidence demonstrates that the dysregulated metabolic enzymes can accelerate tumorigenesis and progression via both nonmetabolic functions. Further elucidation of role in EGFR inhibitor resistance metastasis, two leading causes death lung adenocarcinoma, could help improve patient outcomes. Here, we found aberrant upregulation phosphoserine aminotransferase 1 (PSAT1) confers erlotinib tumor metastasis adenocarcinoma. Depletion PSAT1 restored sensitivity to synergistically augmented tumoricidal effect. Mechanistically, inhibition activated ROS-dependent JNK/c-Jun pathway induce cell apoptosis. In addition, interacted with IQGAP1, subsequently activating STAT3-mediated migration independent its activity. Clinical analyses showed expression positively correlated human Collectively, these findings reveal multifunctionality promoting malignancy through activities.Metabolic functions confer promote suggesting therapeutic targeting may attenuate malignant features cancer.

Language: Английский

Citations

39
Moonlighting enzymes: when cellular context defines specificity DOI
Munishwar N. Gupta, Vladimir N. Uversky

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(5)

Published: April 24, 2023

Language: Английский

Citations

36
ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis DOI Creative Commons
Claudia De Vitis,

Anna Martina Battaglia,

Matteo Pallocca

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: March 22, 2023

Metastases are the major cause of cancer-related morbidity and mortality. By time cancer cells detach from their primary site to eventually spread distant sites, they need acquire ability survive in non-adherent conditions proliferate within a new microenvironment spite stressing that may severely constrain metastatic process. In this study, we gained insight into molecular mechanisms allowing an anchorage-independent manner, regardless both tumor-intrinsic variables nutrient culture conditions.3D spheroids derived lung adenocarcinoma (LUAD) breast were cultured either nutrient-rich or -restricted conditions. A multi-omics approach, including transcriptomics, proteomics, metabolomics, was used explore changes underlying transition 2 3D cultures. Small interfering RNA-mediated loss function assays validate role identified differentially expressed genes proteins H460 HCC827 LUAD as well MCF7 T47D cell lines.We found cultures is associated with significant expression involved metabolic reprogramming. particular, observed tumor spheroid growth implies overexpression ALDOC ENO2 glycolytic enzymes concomitant enhanced consumption glucose fructose production lactate. Transfection siRNA against determined reduction lactate production, viability size produced by H460, HCC827, MCF7, lines.Our results show survival supported drive metabolism towards production. Notably, finding valid for all lines have analyzed different environmental broader Validation mechanism other origin will be necessary broaden types. Future vivo studies assess metastasis.

Language: Английский

Citations

26