Functional interaction between co-expressed MAGE-A proteins

Laiseca, Julieta Eva; Ladelfa, María Fátima; Cotignola, Javier; Peche, Leticia Y.; Pascucci, Franco Andrés; Castaño, Bryan Alain Alexis; Galigniana, Mario D.; Schneider, Claudio; Monte, Martín

doi:10.1371/journal.pone.0178370

Cited by 12 publications

(16 citation statements)

References 33 publications

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“…This assertion is sustained by the fact that the MAGE family (melanoma antigen genes-A) are expressed both in melanoma and in prostate cancer. In 2017, it was demonstrated that MAGE-A proteins can potentiate specific oncogenic processes being involved in several unrelated cancers due to the complex MAGE gene network [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine Pattern Is Sex-Dependent in Mouse Cutaneous Melanoma Experimental Model

Surcel

Constantin

Căruntu

et al. 2017

Journal of Immunology Research

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We present the evaluation of inflammatory cytokines in mouse cutaneous melanoma experimental model, as markers of disease evolution. Moreover, to test our experimental model, we have used low doses of dacarbazine (DTIC). C57 BL/6J mouse of both sexes were subjected to experimental cutaneous melanoma and treated with low doses of DTIC. Clinical parameters and serum cytokines were followed during tumor evolution and during DTIC therapy. Cytokine/chemokine pattern was assessed using xMAP technology and the following molecules were quantified: interleukins (IL)-1-beta, IL-6, IL-10, IL-12 (p70), interferon (IFN)-gamma, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein (MCP-1), and keratinocyte-derived chemokine (KC). Significant differences were found between normal females and males mice, female mice having a statistically higher serum concentration of IL-1-beta compared to male mice, while males have a significantly higher concentration of MIP-1-alpha. During melanoma evolution in the female group, IL-1-beta, MIP-1-alpha, and KC circulatory levels were found 10-fold increased, while other cytokines doubled their values. In the male mice group, only circulatory KC increased 4 times, while IL-1-beta and TNF-alpha doubled their circulatory values. Various serum cytokines correlated with the disease evolution in cutaneous melanoma mouse model.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine Pattern Is Sex-Dependent in Mouse Cutaneous Melanoma Experimental Model

Surcel

Constantin

Căruntu

et al. 2017

Journal of Immunology Research

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“…However, suppressing MAGEA12 expression decreased the migratory and invasive capacities of both cell lines, notwithstanding the differences between the lines in terms of migration and invasion (Figure 4b,c). In addition, we showed that MAGEA12 silencing reduced breast cancer aggressiveness by using a 3D culture system that can identify aggressive characteristics based on a cell shape classification [32][33][34]. Thus, siRNA-mediated MAGEA12 knockdown not only dramatically reduced the expression of MAGEA12, but it also changed the morphology of the cell clusters from their usual aggressive grape-like phenotype to the less aggressive rounded/mass cluster phenotype (Figure 4d).…”

Section: Effect Of Magea12 Silencing and Overexpression On Breast Cancer Cell Aggressivenessmentioning

confidence: 87%

“…This may reflect their close location on the X chromosome [29,30]. In particular, MAGEA3 and MAGEA6 expression are highly correlated in colon and lung cancer [31], as is MAGEA6 and MAGEA11 expression in prostate cancer [32]. However, it is not clear whether, and which, MAGE-A members are simultaneously expressed in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness

Kim

et al. 2021

Cancers

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After decades-long efforts to diagnose and treat breast cancer, the management strategy that has proved most successful to date is molecular-subtype-specific inhibition of the hormone receptors and HER2 that are expressed by individual cancers. Melanoma-associated antigen (MAGE) proteins comprise >40 highly conserved members that contain the MAGE homology domain. They are often overexpressed in multiple cancers and contribute to cancer progression and metastasis. However, it remains unclear whether the biological activity arising from MAGE gene expression is associated with breast cancer subtypes. In this study, we analyzed the RNA-sequencing (RNA-seq) data of 70 breast cancer cell lines and found that MAGEA12 and MAGEA3 were highly expressed in a subset of these lines. Significantly, MAGEA12 and MAGEA3 expression levels were independent of hormone receptor expression levels but were closely associated with markers of active histone modifications. This indicates that overexpression of these genes is attributable to epigenetic deregulation. RNA-seq of MAGEA12-depleted cells was then used to identify 382 candidate targets of MAGEA12 that were downregulated by MAGEA12 depletion. Furthermore, our gain-of-function experiments showed that MAGEA12 overexpression promoted aggressive behaviors of malignant breast cancer cells, including enhancing their cell migration and invasion. These changes were associated with increased epigenetic deregulation of the MAGEA12 signature genes. Thus, MAGEA12 may play an important role in breast cancer malignancy. Taken together, our findings suggest that MAGEA12 could be a promising therapeutic target in breast cancer, and its overexpression and epigenetic changes could serve as subtype classification biomarkers.

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“…Theoretically, co-expression of structurally similar MAGE proteins can regulate a large number of oncogenic functions. Nevertheless, functional interaction of two MAGE proteins to perform a single oncogenic function has also been reported ( 43 ). Furthermore, both MAGEH1 and Necdin have been shown to interact with p75 neurotrophin receptors, a class of receptors that regulate cell growth and neuronal survival ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma

et al. 2020

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Melanoma associated antigen (MAGE) is an extensively studied family of tumor-associated genes that share a common MAGE homology domain (MHD). Based upon their expression pattern, MAGE genes have been broadly classified into type 1 MAGEs (T1Ms) and type 2 MAGEs (T2Ms) categories. Interestingly, several T2Ms are highly expressed in the brain and involved in the regulation of neuronal development, differentiation, and survival. Available literature suggests possible tumor suppressor functions of a few T2Ms, while information available about their expression, regulation, and clinical significance in glioma is scanty. This prompted us to perform a comprehensive analysis of T2M expression in glioma. Gene expression data from glioma datasets: Oncomine, TCGA, and REMBRANDT study, were used to assess the mRNA expression of T2M genes (MAGED1, MAGED2, MAGED3, MAGED4, MAGED4B, MAGEE1, MAGEE2, MAGEF1, MAGEH1, MAGEL2, NSMCE3, and NDN), and their association with clinical characteristics and composition of the tumor microenvironment. Further, mutation, copy number alteration, and DNA methylation data from TCGA were assessed for determining potential mechanisms of T2Ms expression in glioma. Expression analysis revealed overexpression of MAGED subfamily genes in glioma, while other genes of this family exhibited reduced expression in advanced grades of this malignancy. Further, the expression of T2Ms exhibited varying extent of positive correlations with each other. Amongst downregulated T2Ms, MAGEH1 expression exhibited negative correlations with DNA methylation. Additionally, genes associated with MAGEH1 were enriched in Myc and Hedgehog signaling. Furthermore, T2Ms downregulation was associated with immune infiltration in glioma tissues and poor overall survival of glioma patients. In multivariate Cox regression analysis, MAGEH1 emerged as an independent prognosticator in lower grade glioma. Conclusively, these results suggest that expression of T2Ms is associated with important clinical and molecular features in glioma. Mechanistic studies may further provide novel insights into their role in glioma progression.

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Functional interaction between co-expressed MAGE-A proteins

Cited by 12 publications

References 33 publications

Inflammatory Cytokine Pattern Is Sex-Dependent in Mouse Cutaneous Melanoma Experimental Model

Inflammatory Cytokine Pattern Is Sex-Dependent in Mouse Cutaneous Melanoma Experimental Model

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness

Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma

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