2013
DOI: 10.1038/jid.2012.355
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MAGE-C2 Promotes Growth and Tumorigenicity of Melanoma Cells, Phosphorylation of KAP1, and DNA Damage Repair

Abstract: Melanoma-associated antigen-encoding (MAGE) genes are expressed in melanoma and other cancers but not in normal somatic cells. MAGE expression is associated with aggressive tumor growth, poor clinical outcome, and resistance to chemotherapy, but the mechanisms have not been completely elucidated. In this study, we show that downregulation of MAGE-C2 in A375 melanoma cells and low-passage cultures from human metastatic melanomas (MRA cells) results in increased apoptosis and decreased growth of tumor xenografts… Show more

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Cited by 51 publications
(57 citation statements)
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“…Although the current view in the field is that ATM and ATR signaling inhibits tumor progression rather than promoting cancer (Bartkova et al, 2006;Gorgoulis et al, 2005;Halazonetis et al, 2008), there has been a number of recent reports of overexpression of ATM or ATR, or of activation of the downstream pathways in different cancers (Albiges et al, 2014;Bhatia et al, 2013;Hoglund et al, 2011;Mahajan et al, 2012;Sarmento et al, 2015;Tho et al, 2012;Vadnais et al, 2012;Verlinden et al, 2007;Xu et al, 2013) (see poster). Of note, the addition of an extra allele of Chk1 has even been found to promote Ras-or E1A-mediated transformation more efficiently in comparison to such transformation of wild-type littermates (Lopez-Contreras et al, 2012), suggesting that the ATR-Chk1 axis has a pro-malignant transformation role.…”
Section: Box 1 Relevance Of Atm and Atr Signaling In Cancermentioning
confidence: 99%
“…Although the current view in the field is that ATM and ATR signaling inhibits tumor progression rather than promoting cancer (Bartkova et al, 2006;Gorgoulis et al, 2005;Halazonetis et al, 2008), there has been a number of recent reports of overexpression of ATM or ATR, or of activation of the downstream pathways in different cancers (Albiges et al, 2014;Bhatia et al, 2013;Hoglund et al, 2011;Mahajan et al, 2012;Sarmento et al, 2015;Tho et al, 2012;Vadnais et al, 2012;Verlinden et al, 2007;Xu et al, 2013) (see poster). Of note, the addition of an extra allele of Chk1 has even been found to promote Ras-or E1A-mediated transformation more efficiently in comparison to such transformation of wild-type littermates (Lopez-Contreras et al, 2012), suggesting that the ATR-Chk1 axis has a pro-malignant transformation role.…”
Section: Box 1 Relevance Of Atm and Atr Signaling In Cancermentioning
confidence: 99%
“…MAGE-C2 can be degraded into nonapeptide or decapeptide in the cytoplasm of tumor cells and combine with HLA molecules in the cells as the epitope, which is subsequently presented on the cell membrane, inducing the body's immune system to produce relevant antibodies [5]. It has been verified that abnormal expression of MAGE-C2 can be found in adenocarcinomas of lung cancer, liver cancer, laryngocarcinoma, prostate cancer, and non-TNBC [69]. However, there is little research on the relationship between MAGE-C2 and TNBC.…”
Section: Introductionmentioning
confidence: 99%
“…We and others have shown that MAGE expression enhances KAP1 ubiquitin ligase activity and specifically increases ubiquitination and degradation of p53 (Bhatia et al, 2013; Monte et al, 2006; Xiao et al, 2011). We have also shown that MAGE-C2 increases KAP1 mediated ubiquitination and degradation of ZNF382.…”
Section: Resultsmentioning
confidence: 82%
“…Class I MAGE proteins are characterized by nearly identical MAGE homology domains (MHDs) containing two highly conserved leucines that we and others have shown are necessary for binding to KAP1 (Bhatia et al, 2013; Doyle et al, 2010). In particular, we have shown that they are necessary for the regulatory affects of MAGE-C2 on ZNF382 function and ubiquitination.…”
Section: Discussionmentioning
confidence: 99%
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