Serine metabolism orchestrates macrophage polarization by regulating the IGF1–p38 axis

Shan, Xiaonan; Hu, Penghui; Ni, Lina; Shen, Long; Zhang, Yanan; Ji, Zemin; Cui, Yan; Guo, Meihua; Wang, Haoan; Ran, Ling; Yang, Kun; Wang, Ting; Wang, Lei; Chen, Bin; Yao, Zhi; Wu, Yingjie; Yu, Qiujing

doi:10.1038/s41423-022-00925-7

Cited by 55 publications

(30 citation statements)

References 56 publications

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“…Serine metabolism supports macrophage produce IL-1β, which contributes to the immunosuppression in breast cancer [82,83]. Suppressing serine metabolism enhances the polarization of interferon-γ-activated macrophages (M(IFN-γ)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) by regulating the IGF1-p38 axis [84]. Recent evidence suggests that serine/glycine metabolism is not only an important driver of macrophage function [82][83][84] and revascularization [85,86], but also contributes to the maintenance of CSCs in the TME.…”

Section: Serine/glycine Metabolismmentioning

confidence: 99%

“…Suppressing serine metabolism enhances the polarization of interferon-γ-activated macrophages (M(IFN-γ)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) by regulating the IGF1-p38 axis [84]. Recent evidence suggests that serine/glycine metabolism is not only an important driver of macrophage function [82][83][84] and revascularization [85,86], but also contributes to the maintenance of CSCs in the TME. Silencing of PHGDH leads to downregulation of transcriptional regulators involved in self-renewal and pluripotency (e g. Oct4, Nanog, Sox2, Bmi1), reducing the formation of embryonic and breast CSCs [87].…”

Section: Serine/glycine Metabolismmentioning

confidence: 99%

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Novel insight into metabolic reprogrammming in cancer radioresistance: A promising therapeutic target in radiotherapy

Yu¹,

Yu²,

Ge³

et al. 2023

Int. J. Biol. Sci.

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Currently, cancer treatment mainly consists of surgery, radiotherapy, chemotherapy, immunotherapy, and molecular targeted therapy, of which radiotherapy is one of the major pillars. However, the occurrence of radioresistance largely limits its therapeutic effect. Metabolic reprogramming is an important hallmark in cancer progression and treatment resistance. In radiotherapy, DNA breakage is the major mechanism of cell damage, and in turn, cancer cells are prone to increase the metabolic flux of glucose, glutamine, serine, arginine, fatty acids etc., thus providing sufficient substrates and energy for DNA damage repair. Therefore, studying the linkage between metabolic reprogramming and cancer radioresistance may provide new ideas for improving the efficacy of tumor therapy. This review mainly focuses on the role of metabolic alterations, including glucose, amino acid, lipid, nucleotide and other ion metabolism, in radioresistance, and proposes possible therapeutic targets to improve the efficacy of cancer radiotherapy.

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Section: Serine/glycine Metabolismmentioning

confidence: 99%

Section: Serine/glycine Metabolismmentioning

confidence: 99%

Novel insight into metabolic reprogrammming in cancer radioresistance: A promising therapeutic target in radiotherapy

Yu¹,

Yu²,

Ge³

et al. 2023

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…Shan et al. 87 showed that inhibition of serine metabolism, either by inhibiting the activity of phosphoglycerate dehydrogenase, a key enzyme in the serine biosynthesis pathway, or by limiting exogenous serine and glycine, significantly enhanced the polarisation of M(IFN‐γ). However, it inhibited the polarisation of M(IL‐4).…”

Section: Macrophage Metabolic Reprogramming Endogenously Drivenmentioning

confidence: 99%

“…86 In addition, recent studies have found that serine and citrulline are associated with macrophage activation. Shan et al 87 showed that inhibition of serine metabolism, either by inhibiting the activity of phosphoglycerate dehydrogenase, a key enzyme in the serine biosynthesis pathway, or by limiting exogenous serine and glycine, significantly enhanced the polarisation of M(IFN-γ). However, it inhibited the polarisation of M(IL-4).…”

Section: Reprogramming Of Amino Acid Metabolismmentioning

confidence: 99%

Macrophage metabolic reprogramming and atherosclerotic plaque microenvironment: Fostering each other?

Xiao

Hou

Xie

et al. 2023

Clinical & Translational Med

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Macrophages are the central immune cells in atherosclerosis (AS) and play a critical role in the initiation, progression and invasion of atherosclerotic plaques. Metabolic reprogramming is a crucial feature that determines macrophage function and is driven by a combination of intrinsic alterations in macrophages and extrinsic factors such as cytokines acting in the plaque microenvironment. Intrinsic macrophage mechanisms activate signal transduction pathways that change metabolic enzyme activity, and the expression of metabolic regulators. Extrinsic signalling mechanisms involve lipids and cytokines in the microenvironment, promoting and amplifying macrophage metabolic reprogramming. This review describes the intrinsic and extrinsic mechanisms driving macrophage metabolic reprogramming in the AS microenvironment and the interplay of these metabolic rewires in the microenvironment. Moreover, we discuss whether targeting these different pathways to treat macrophage microenvironmental changes can alter the fate of the vulnerable plaques.

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“…CRGs affect tumorigenesis, invasion, and metastasis in a manner similar to ferroptosis and pyroptosis genes. cuproptosis is closely related to the progression of cancer and is a potential new therapeutic target for the targeted killing of cancer cells [ 4 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Leveraging a cuproptosis-based signature to predict the prognosis and drug sensitivity of cutaneous melanoma

Yang

Zhang

et al. 2023

J Transl Med

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Immunotherapy is a vital treatment for patients with cutaneous melanoma (CM), but effective predictors to guide clinical immunotherapy are lacking. Cuproptosis is a newly discovered mode of cell death related to tumorigenesis. Exploring the relationship between the mode of cuproptosis and the effect of immunotherapy on CM could better guide clinical management. We clustered all patients with CM in the Cancer Genome Atlas (TCGA) database based on cuproptosis-related genes (CRGs). Prognosis, immunotherapeutic effect, tumor microenvironment score, expression of CD274, CTLA4, and PDCD1, and abundance of CD8 + T infiltration in group A were higher than in group B. Using a combination of LASSO and COX regression analysis, we identified 10 molecules significant to prognosis from differentially expressed genes between the two groups and constructed a cuproptosis-related scoring system (CRSS). Compared with the American Joint Committee on Cancer (AJCC) staging system, CRSS more accurately stratified CM patient risk and guided immunotherapy. CRSS successfully stratified risk and predicted the effect of immunotherapy in 869 patients with eight CM immunotherapy datasets and multiple other tumor immunotherapy cohorts. The nomogram model, which combined AJCC stage and CRSS, greatly improved the ability and accuracy of prognosis prediction. In general, our cuproptosis-related scoring system and nomogram model accurately stratified risk in CM patients and effectively predicted prognosis and the effect of immunotherapy in CM patients.

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Serine metabolism orchestrates macrophage polarization by regulating the IGF1–p38 axis

Cited by 55 publications

References 56 publications

Novel insight into metabolic reprogrammming in cancer radioresistance: A promising therapeutic target in radiotherapy

Novel insight into metabolic reprogrammming in cancer radioresistance: A promising therapeutic target in radiotherapy

Macrophage metabolic reprogramming and atherosclerotic plaque microenvironment: Fostering each other?

Leveraging a cuproptosis-based signature to predict the prognosis and drug sensitivity of cutaneous melanoma

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