GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer

Yang, Yan; He, Xin; Tang, Qianqian; Shao, You-Cheng; Song, Wenjing; Gong, Peng; Zeng, Yifan; Huang, Shu‐Chun; Zhou, Jiang-Yao; Wan, Huifang; Zhang, Jingwei

doi:10.3389/fonc.2021.629633

Cited by 5 publications

(4 citation statements)

References 40 publications

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“…Therefore, it is reasonable to consider whether the findings reported in our study may also apply in other types of tumor stem cells. Given that in certain studies gmfg was considered as a potential predictive factor in the development of cancer [ 23 , 68 ], the impact of biomechanical microenvironment should be taken into account in the treatment of diseases related to gmfg .…”

Section: Discussionmentioning

confidence: 99%

Glia maturation factor-γ is required for initiation and maintenance of hematopoietic stem and progenitor cells

Luo

Cai

et al. 2023

Stem Cell Res Ther

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Background In vertebrates, hematopoietic stem and progenitor cells (HSPCs) emerge from hemogenic endothelium in the floor of the dorsal aorta and subsequently migrate to secondary niches where they expand and differentiate into committed lineages. Glia maturation factor γ (gmfg) is a key regulator of actin dynamics that was shown to be highly expressed in hematopoietic tissue. Our goal is to investigate the role and mechanism of gmfg in embryonic HSPC development. Methods In-depth bioinformatics analysis of our published RNA-seq data identified gmfg as a cogent candidate gene implicated in HSPC development. Loss and gain-of-function strategies were applied to study the biological function of gmfg. Whole-mount in situ hybridization, confocal microscopy, flow cytometry, and western blotting were used to evaluate changes in the number of various hematopoietic cells and expression levels of cell proliferation, cell apoptosis and hematopoietic-related markers. RNA-seq was performed to screen signaling pathways responsible for gmfg deficiency-induced defects in HSPC initiation. The effect of gmfg on YAP sublocalization was assessed in vitro by utilizing HUVEC cell line. Results We took advantage of zebrafish embryos to illustrate that loss of gmfg impaired HSPC initiation and maintenance. In gmfg-deficient embryos, the number of hemogenic endothelium and HSPCs was significantly reduced, with the accompanying decreased number of erythrocytes, myelocytes and lymphocytes. We found that blood flow modulates gmfg expression and gmfg overexpression could partially rescue the reduction of HSPCs in the absence of blood flow. Assays in zebrafish and HUVEC showed that gmfg deficiency suppressed the activity of YAP, a well-established blood flow mediator, by preventing its shuttling from cytoplasm to nucleus. During HSPC initiation, loss of gmfg resulted in Notch inactivation and the induction of Notch intracellular domain could partially restore the HSPC loss in gmfg-deficient embryos. Conclusions We conclude that gmfg mediates blood flow-induced HSPC maintenance via regulation of YAP, and contributes to HSPC initiation through the modulation of Notch signaling. Our findings reveal a brand-new aspect of gmfg function and highlight a novel mechanism for embryonic HSPC development.

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Section: Discussionmentioning

confidence: 99%

Glia maturation factor-γ is required for initiation and maintenance of hematopoietic stem and progenitor cells

Luo

Cai

et al. 2023

Stem Cell Res Ther

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“…Identified as a critical regulator of cytokine-responsive protein, GMFG has been reportedly essential for various physiopathological processes [ 11 ]. Despite accumulating molecules clarified in cancer tumorigenesis, neither the roles of GMFG and mechanistic details remain enigmatic.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the lessened migratory and invasive capacities of colorectal cancer cells is a consequence of GMFG silence [ 10 ]. However in breast cancer, GMFG is found to be poorly expressed in cancer tissues, dismal clinical outcome are detected in breast patients with low GMFG [ 11 ]. The context-dependent expression of GMFG was also validated by a TCGA pan-cancer analysis which reveals a low expression of GMFG in LUAD and LUSC [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

GMFG (glia maturation factor gamma) inhibits lung cancer growth by activating p53 signaling pathway

2022

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The tumor-promoting or tumor-suppressing functions of Glia maturation factor gamma (GMFG) were described in several cancers. However, how GMFG regulates lung cancer progression is elusive. Bioinformatics analysis was employed to analyze GMFG expression in lung adenocarcinoma (LUAD) and lung squamous cancer (LUSC) as well as its significance in prognosis prediction and diagnosis in lung cancer patients. CCK8 and colony formation assays were adopted to evaluate the impact of GMFG overexpressing and depleting on lung cancer cell proliferation. And in vivo experiments were implemented. Luciferase reporter assays were used to disclose the signaling pathway mediated by GMFG in lung cancer. GMFG expression was lower in LUSC and LUAD tissues compared with normal lung tissues based on TCGA and GTEx databases. Low GMFG expression was associated with lower overall survival and shorter disease specific survival compared high GMFG expression. In vitro loss and gain functions assays demonstrated that ectopically GMFG expression dampened the lung cancer cell proliferation while GMFG knockout escalated the cell proliferation. The promoting effect of GMFG knockout on lung cancer tumorgenesis was also observed in vivo. More interesting, GMFG overexpression reinforced the p53 signaling pathway in lung cancer cells, conversely GMFG deficiency disrupted p53 signaling pathway. In conclusion, we revealed that GMFG is fundamental to p53 signaling pathway to inhibit lung cancer progression, highlighting the importance of GMFG as a p53 inducer for lung cancer patient’s diagnosis and therapy.

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“…GMFG has also been shown to inhibit cellular inflammatory signaling resulting leading to the suppression of monocyte chemotaxis by regulating the recycling of effective B-integrin to plasma membrane ( Aerbajinai et al, 2016 ). It also influences the infiltration of immune cells and immune checkpoints; hence, it may be a novel therapeutic target for cancer treatment ( Yang et al, 2021 ). Lan et al (2021) reported the expression of GMFG in glioma for the first time and found that high expression of GMFG was associated with worse overall survival in glioma.…”

Section: Introductionmentioning

confidence: 99%

Expression and Prognostic Role of Glia Maturation Factor-γ in Gliomas

Liu

Zhu²,

Gao³

et al. 2022

Front. Mol. Neurosci.

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BackgroundGlia maturation factor-γ (GMFG) regulates actin cytoskeletal organization and promotes the invasion of cancer cells. However, its expression pattern and molecular function in gliomas have not been clearly defined.MethodsIn this study, public datasets comprising 2,518 gliomas samples were used to explore GMFG expression and its correlation with malignancy in gliomas. Immunohistochemistry (IHC) staining was performed to determine the expression of GMFG in gliomas using an in-house cohort that contained 120 gliomas samples. Gene ontology enrichment analysis was conducted using the DAVID tool. The correlation between GMFG expression and immune cell infiltration was evaluated using TIMER, Tumor Immune Single-Cell Hub (TISCH) database, and IHC staining assays. The Kaplan–Meier analysis was performed to determine the prognostic role of GMFG and its association with temozolomide (TMZ) response in gliomas.ResultsThe GMFG expression was higher in gliomas compared with non-tumor brain tissues both in public datasets and in-house cohort. High expression of GMFG was significantly associated with WHO grade IV, IDH 1/2 wild-type, and mesenchymal (ME) subtypes. Bioinformatic prediction and IHC analysis revealed that GMFG expression obviously correlated with the macrophage marker CD163 in gliomas. Moreover, both lower grade glioma (LGG) and glioblastoma multiforme (GBM) patients with high GMFG expression had shorter overall survival than those with low GMFG expression. These results indicate that GMFG may be a therapeutic target for the treatment of such patients. Patients with low GMFG expression who received chemotherapy had a longer survival time than those with high GMFG expression. For patients who received ion radiotherapy (IR) only, the GMFG expression level had no effect on the overall survival neither in CGGA and TCGA datasets.ConclusionThe GMFG is a novel prognostic biomarker for patients with both LGG and GBM. Increased GMFG expression is associated with tumor-associated macrophages (TAMs) infiltration and with a bad response to TMZ treatment.

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GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer

Cited by 5 publications

References 40 publications

Glia maturation factor-γ is required for initiation and maintenance of hematopoietic stem and progenitor cells

Glia maturation factor-γ is required for initiation and maintenance of hematopoietic stem and progenitor cells

GMFG (glia maturation factor gamma) inhibits lung cancer growth by activating p53 signaling pathway

Expression and Prognostic Role of Glia Maturation Factor-γ in Gliomas

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