Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner

Wu, Jianqing; Shen, Shuai; Liu, Tianqi; Ren, Xiufang; Zhu, Chen; Liang, Qingyu; Cui, Xiao; Chen, Ling; Peng, Cheng; Cheng, Wen; Wu, Anhua

doi:10.1038/s41388-022-02295-w

Cited by 17 publications

(21 citation statements)

References 88 publications

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“…To investigate whether RARRES2 could have a similar effect on other CSCs, we focused on the role of the IGF1–RARRES2 axis in the TAM–CSC interaction by restoring intercellular communication. The chemerin/CMKLR1 axis promotes the interaction between glioblastoma (GBM) cells and TAMs by activating NF-κB signaling 75 . In addition, previous studies have shown that TAMs can promote metastasis and help maintain the stemness of thyroid cancer cells by secreting IGF 76 .…”

Section: Discussionmentioning

confidence: 99%

RARRES2 is involved in the “lock-and-key” interactions between osteosarcoma stem cells and tumor-associated macrophages

Ma,

Chen,

et al. 2024

Sci Rep

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Osteosarcoma (OS) is a type of tumor. Osteosarcoma stem cells (OSCs) are responsible for drug resistance, recurrence, and immunosuppression in OS. We aimed to determine the heterogeneity of OSCs and the immunosuppression mechanisms underlying the interactions between OSCs and tumor-associated macrophages (TAMs). The cell components, trajectory changes, and cell communication profiles of OS cells were analyzed by transcriptomics at the single-cell level. The intercellular communication patterns of OSCs were verified, and the role of the cell hub genes was revealed. Hub geneS are genes that play important roles in regulating certain biological processes; they are often defined as the genes with the strongest regulatory effect on differentially expressed gene sets. Moreover, various cellular components of the OS microenvironment were identified. Malignant cells were grouped, and OSCs were identified. Further regrouping and communication analysis revealed that the genes in the stemness maintenance and differentiation subgroups were involved in communication with macrophages. Key receptor–ligand pairs and target gene sets for cell communication were obtained. Transcriptome data analysis revealed the key gene RARRES2, which is involved in intercellular communication between OSCs and TAMs. In vitro studies confirmed that macrophages promote RARRES2-mediated stemness maintenance in OSCs via the TAM-secreted cytokine insulin-like growth factor 1. Patient studies confirmed that RARRES2 could be a biomarker of OS. OSCs are highly heterogeneous, and different subgroups are responsible for proliferation and communication with other cells. The IGF-RARRES2 axis plays a key role in maintaining OSC stemness through communication with TAMs.

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Section: Discussionmentioning

confidence: 99%

RARRES2 is involved in the “lock-and-key” interactions between osteosarcoma stem cells and tumor-associated macrophages

Ma,

Chen,

et al. 2024

Sci Rep

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“…The results indicated that RARRES2 knockdown can significantly reduce GBM cell viability and proliferation activity, and the protein expression level of RARRES2 was significantly correlated with IDH status in GBM patients. Although RARRES2 has different expression patterns in different tumors, RARRES2 can promote GBM mesenchymal properties by inhibiting the ubiquitin‒proteasome degradation of CMKLR1 [ 42 ], which indicates that RARRES2 can support tumor progression in GBM. Our results also demonstrated that the expression of RARRES2 in GBM was positively correlated with TME scores and M0 macrophage infiltration and positively correlated with the expression of immune checkpoints, such as PD-L1 (CD274).…”

Section: Discussionmentioning

confidence: 99%

Targeting copper death genotyping associated gene RARRES2 suppresses glioblastoma progression and macrophages infiltration

Yan

Meng

et al. 2023

Cancer Cell Int

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Background Copper homeostasis is associated with malignant biological behavior in various tumors. The excessive accumulation of copper can induce tumor death, which is named cuproptosis, and it is also closely related to tumor progression and the formation of the immune microenvironment. However, the associations of cuproptosis with glioblastoma (GBM) prognosis and microenvironment construction are poorly understood. Method First, TCGA and GEO (GSE83300, GSE74187) merged datasets were used to analyze the association of cuproptosis-related genes (CRGs) with GBM. Then, we performed cluster analysis of CRGs in GBM from the GEO (GSE83300, GSE74187) and TCGA merged datasets. Subsequently, the prognostic risk model was constructed by least absolute shrinkage and selection operator (LASSO) according to gene expression features in CRG clusters. Next, we performed a series of in-depth analyses, including tumor mutational burden (TMB) analysis, cluster analysis, and GBM IDH status prediction. Finally, RARRES2 was identified as a target gene for GBM treatment, especially IDH wild-type GBM. In addition, we further analyzed the correlation of CRG clusters and RARRES2 expression with the GBM immune microenvironment by ESTIMATE and CIBERSORT analyses. In vitro experiments were conducted to demonstrate that targeting RARRES2 inhibits glioblastoma progression and macrophage infiltration, particularly IDH wild-type GBM. Results In the present study, we demonstrated that the CRG cluster was closely related to GBM prognosis and immune cell infiltration. Moreover, the prognostic risk model constructed with the three genes (MMP19, G0S2, RARRES2) associated with the CRG clusters could well evaluate the prognosis and immune cell infiltration in GBM. Subsequently, after further analyzing the tumor mutational burden (TMB) in GBM, we confirmed that RARRES2 in the prognostic risk model could be used as a crucial gene signature to predict the prognosis, immune cell infiltration and IDH status of GBM patients. Conclusion This study fully revealed the potential clinical impact of CRGs on GBM prognosis and the microenvironment, and determined the effect of the crucial gene (RARRES2) on the prognosis and tumor microenvironment construction of GBM, meanwhile, our study also revealed over-expressed RARRES2 is related to the IDH satus of GBM, which provides a novel strategy for the treatment of GBM, particularly IDH wild-type GBM.

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“…The detailed protocol of flow cytometry was performed as previously described ( 51 ). FACS data were analyzed through FlowJo software (version 10.4).…”

Section: Methodsmentioning

confidence: 99%

Molecular profiling identifies distinct subtypes across TP53 mutant tumors

Chen¹,

Liu²,

Wu³

et al. 2022

JCI Insight

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TP53 mutation (TP53mut) is one of the most important driver events facilitating tumorigenesis, which could induce a series of chain reactions to promote tumor malignant transformation. However, the malignancy progression patterns under TP53 mutation still remain less known. Clarifying the molecular landscapes of TP53mut tumors will help us understand the process of tumor development and aid precise treatment. Here, we distilled genetic and epigenetic features altered in TP53mut cancers for cluster-of-cluster analysis. Using integrated classification, we derived five different subtypes of TP53mut patients. These subtypes have distinct features in genomic alteration, clinical relevance, microenvironment dysregulation and potential therapeutics. Among the five subtypes, COCA3 was identified as the subtype with worst prognosis, causing an immunosuppressive microenvironment and immunotherapeutic resistantance. Further drug efficacy research highlighted olaparib as the most promising therapeutic agents for COCA3 tumors. Importantly, the therapeutic efficacy of olaparib in COCA3 and immunotherapy in non-COCA3 tumors was validated in vivo experiment. Summarily, our study first explored the important molecular events and developed a subtype classification system with distinct targeted therapy strategies for different subtypes of TP53mut tumors. These multi-omics classification systems provided a valuable resource that significantly expands the knowledge of TP53mut tumors and might eventually benefit in clinical practice.

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Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner

Cited by 17 publications

References 88 publications

RARRES2 is involved in the “lock-and-key” interactions between osteosarcoma stem cells and tumor-associated macrophages

RARRES2 is involved in the “lock-and-key” interactions between osteosarcoma stem cells and tumor-associated macrophages

Targeting copper death genotyping associated gene RARRES2 suppresses glioblastoma progression and macrophages infiltration

Molecular profiling identifies distinct subtypes across TP53 mutant tumors

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