SENP3 loss promotes M2 macrophage polarization and breast cancer progression

Xiao, Ming; Bian, Qian; Lao, Yimin; Yi, Jing; Sun, Xun; Sun, Xuxu; Yang, Jie

doi:10.1002/1878-0261.12967

Cited by 43 publications

(28 citation statements)

References 47 publications

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“…SUMO also influences the activity of NF-κB signaling regulators, NEMO and IκBα, affecting immune response activation [158][159][160][161][162]. SENP3-mediated deSUMOylation regulates antitumor immune response functions of Tregs, macrophages, and dendritic cells [163][164][165]. The loss of SENP3 deSUMOylase activity in Tregs results in dysregulation T-cell homeostasis and SENP3 deficiency in macrophages facilitates macrophage polarization towards the pro-tumor M2 subtype.…”

Section: Sumoylation In Cellular Processes Relevant For Cancermentioning

confidence: 99%

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Kukkula

Ojala

Mendez

et al. 2021

Cancers

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SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Key oncoproteins and tumor suppressors are SUMO substrates. In addition to alterations in SUMO pathway activity due to conditions typically present in cancer, such as hypoxia, the SUMO machinery components are deregulated at the genomic level in cancer. The delicate balance between SUMOylation and deSUMOylation is regulated by SENP enzymes possessing SUMO-deconjugation activity. Dysregulation of SUMO machinery components can disrupt the balance of SUMOylation, contributing to the tumorigenesis and drug resistance of various cancers in a context-dependent manner. Many molecular mechanisms relevant to the pathogenesis of specific cancers involve SUMO, highlighting the potential relevance of SUMO machinery components as therapeutic targets. Recent advances in the development of inhibitors targeting SUMOylation and deSUMOylation permit evaluation of the therapeutic potential of targeting the SUMO pathway in cancer. Finally, the first drug inhibiting SUMO pathway, TAK-981, is currently also being evaluated in clinical trials in cancer patients. Intriguingly, the inhibition of SUMOylation may also have the potential to activate the anti-tumor immune response. Here, we comprehensively and systematically review the recent developments in understanding the role of SUMOylation in cancer and specifically focus on elaborating the scientific rationale of targeting the SUMO pathway in different cancers.

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Section: Sumoylation In Cellular Processes Relevant For Cancermentioning

confidence: 99%

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Kukkula

Ojala

Mendez

et al. 2021

Cancers

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“…In this study, we established FAI using the focal adhesion gene and found that it was closely related to M2 macrophage infiltration. M2 macrophage markers CD163 (Yamaguchi et al, 2016) and MRC1 (Xiao et al, 2021) were also observed to be significantly higher in the high FAI group than in the low FAI group. EMT signaling is a key factor for tumor resistance, regulation of angiogenesis, and promotion of growth (Sabbah et al, 2008;Banias et al, 2020).…”

Section: Discussionmentioning

confidence: 83%

Cross-Talk of Focal Adhesion-Related Gene Defines Prognosis and the Immune Microenvironment in Gastric Cancer

Mao

Chen

et al. 2021

Front. Cell Dev. Biol.

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Background: Focal adhesion, as the intermediary between tumor cells and extracellular matrix communication, plays a variety of roles in tumor invasion, migration, and drug resistance. However, the potential role of focal adhesion-related genes in the microenvironment, immune cell infiltration, and drug sensitivity of gastric cancer (GC) has not yet been revealed.Methods: The genetic and transcriptional perspectives of focal adhesion-related genes were systematically analyzed. From a genetic perspective, the focal adhesion index (FAI) was constructed based on 18 prognosis-related focus adhesion-related genes to evaluate the immune microenvironment and drug sensitivity. Then three prognosis-related genes were used for consistent clustering to identify GC subtypes. Finally, use FLT1, EGF, COL5A2, and M2 macrophages to develop risk signatures, and establish a nomogram together with clinicopathological characteristics.Results: Mutations in the focal adhesion-related gene affect the survival time and clinical characteristics of GC patients. FAI has been associated with a shorter survival time, immune signaling pathways, M2 macrophage infiltration, epithelial-mesenchymal transition (EMT) signaling, and diffuse type of GC. FAI recognizes ALK, cell cycle, and BMX signaling pathways inhibitors as sensitive agents for the treatment of GC. FLT1, EGF, and COL5A2 may distinguish GC subtypes. The established risk signature is of great significance to the prognostic evaluation of GC based on FLT1, EGF, and COL5A2 and M2 macrophage expression.Conclusion: The focal adhesion-related gene is a potential biomarker for the evaluation of the immune microenvironment and prognosis. This work emphasizes the potential impact of the focal adhesion pathway in GC therapy and highlights its guiding role in prognostic evaluation.

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“… 188 IFN‐γ induced by viral infection acted on Toll‐like receptor signaling in macrophages and initiated mitochondria‐driven cell death. 189 , 190 In this process, nitric oxide synthase was induced to promote caspase‐8 cleavage and activate mitochondrial apoptotic effectors. Importantly, the mitochondria‐driven apoptosis potentially increased disease severity in COVID‐19 patients.…”

Section: Mechanisms Of Remodeling Host Metabolism By Sars‐cov‐2mentioning

confidence: 99%

COVID‐19 metabolism: Mechanisms and therapeutic targets

Wang

Cao

Zhang³

et al. 2022

MedComm

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS‐CoV‐2‐induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID‐19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS‐CoV‐2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID‐19 metabolism. SARS‐CoV‐2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS‐CoV‐2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID‐19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS‐CoV‐2‐induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID‐19 pandemic.

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SENP3 loss promotes M2 macrophage polarization and breast cancer progression

Cited by 43 publications

References 47 publications

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Cross-Talk of Focal Adhesion-Related Gene Defines Prognosis and the Immune Microenvironment in Gastric Cancer

COVID‐19 metabolism: Mechanisms and therapeutic targets

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