Copper chaperone ATOX1 is required for MAPK signaling and growth in <i>BRAF</i> mutation-positive melanoma

Kim, Ye Jin; Bond, Gavin J.; Tsang, Tiffany; Posimo, Jessica M.; Busino, Luca; Brady, Donita C.

doi:10.1039/c9mt00042a

Cited by 50 publications

(44 citation statements)

References 59 publications

(72 reference statements)

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“…6 ). To further explore the potential association of hub genes with UC-associated carcinogenesis, a brief literature review was performed to search for the proof of their carcinogenic effects ( Bruggemann et al, 2017 ; Byeon et al, 2010 ; Chung et al, 2017 ; Ciccarone et al, 2020 ; Ding et al, 2020 ; Jana et al, 2020 ; Karginova et al, 2019 ; Khalil, 2007 ; Kim et al, 2019 ; Laiho et al, 2003 ; Li et al, 2019 ; Linehan et al, 2019 ; Liu et al, 2018 ; Millan & Huerta, 2009 ; Oehler et al, 2009 ; Perera et al, 2015 ; Rao et al, 2019 ; Seth et al, 2009 ; Thedieck et al, 2007 ; Viola et al, 2017 ; Wang et al, 2013 ; Wang et al, 2020 ). The results are presented in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis

Zhang

Yan

Han

et al. 2021

PeerJ

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Background Ulcerative colitis-associated colorectal cancer (UC-CRC) is a life-threatening complication of ulcerative colitis (UC). The mechanisms underlying UC-CRC remain to be elucidated. The purpose of this study was to explore the key genes and biological processes contributing to colitis-associated dysplasia (CAD) or carcinogenesis in UC via database mining, thus offering opportunities for early prediction and intervention of UC-CRC. Methods Microarray datasets (GSE47908 and GSE87466) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between groups of GSE47908 were identified using the “limma” R package. Weighted gene co-expression network analysis (WGCNA) based on DEGs between the CAD and control groups was conducted subsequently. Functional enrichment analysis was performed, and hub genes of selected modules were identified using the “clusterProfiler” R package. Single-gene gene set enrichment analysis (GSEA) was conducted to predict significant biological processes and pathways associated with the specified gene. Results Six functional modules were identified based on 4929 DEGs. Green and blue modules were selected because of their consistent correlation with UC and CAD, and the highest correlation coefficient with the progress of UC-associated carcinogenesis. Functional enrichment analysis revealed that genes of these two modules were significantly enriched in biological processes, including mitochondrial dysfunction, cell-cell junction, and immune responses. However, GSEA based on differential expression analysis between sporadic colorectal cancer (CRC) and normal controls from The Cancer Genome Atlas (TCGA) indicated that mitochondrial dysfunction may not be the major carcinogenic mechanism underlying sporadic CRC. Thirteen hub genes (SLC25A3, ACO2, AIFM1, ATP5A1, DLD, TFE3, UQCRC1, ADIPOR2, SLC35D1, TOR1AIP1, PRR5L, ATOX1, and DTX3) were identified. Their expression trends were validated in UC patients of GSE87466, and their potential carcinogenic effects in UC were supported by their known functions and other relevant studies reported in the literature. Single-gene GSEA indicated that biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to angiogenesis and immune response were positively correlated with the upregulation of TFE3, whereas those related to mitochondrial function and energy metabolism were negatively correlated with the upregulation of TFE3. Conclusions Using WGCNA, this study found two gene modules that were significantly correlated with CAD, of which 13 hub genes were identified as the potential key genes. The critical biological processes in which the genes of these two modules were significantly enriched include mitochondrial dysfunction, cell-cell junction, and immune responses. TFE3, a transcription factor related to mitochondrial function and cancers, may play a central role in UC-associated carcinogenesis.

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Section: Resultsmentioning

confidence: 99%

Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis

Zhang

Yan

Han

et al. 2021

PeerJ

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“…A potential explanation for this distinction is that the increased ATOX1 expression in ERpositive tumors influences mitogen-activated protein kinase (MAPK) signaling, perhaps via the ATOX1-ATP7A-lysyl oxidase (LOX) axis [6], which in turn promotes tumor growth and metastasis. In support of such a link, ATOX1 knockout in B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation-positive melanoma cells was found to reduce MAPK signaling [14]. In ER-negative tumors, other pathways (not dependent on ATOX1 levels) may instead define cancer progression [15].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of copper chaperone ATOX1 as prognostic biomarker in breast cancer

2020

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Copper is involved in different hallmarks of cancer, including metastasis, but responsible copper-binding proteins and pathways are not clear. The copper chaperone ATOX1 was recently shown to play a role in breast cancer cell migration, which is a key step in metastasis. Since most cancer-related deaths are due to metastasis, we hypothesized that ATOX1 mRNA expression may be associated with breast cancer disease progression and thus, a prognostic biomarker in breast cancer. We therefore studied the association of ATOX1 expression levels with clinicopathological parameters and survival for 1904 breast cancer patients using the METABRIC data set. Our results indicate ATOX1 expression levels as a potential prognostic biomarker for ER-positive subtypes and early stages of breast cancer. Pre-clinical studies and clinical trials are desired to identify the molecular roles of ATOX1 in these conditions.

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“…The genes might have been implicated in poor prognosis and recurrence of patients with UVM. To be speci c, it is identi ed that copper chaperone ATOX1 is required for MAPK signaling and growth in BRAF mutation-positive melanoma [30]. The mitochondrial ribosomal protein of the small subunits 34 (MRPS34) is explored to compromise protein synthesis and in uence mitochondrial dysfunction [31].…”

Section: Discussionmentioning

confidence: 99%

CIB1 as a potential diagnosis and prognosis biomarker in uveal melanoma

Wang

Liu

Guo

et al. 2020

Preprint

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BackgroundUveal melanoma (UVM) is the most common primary intraocular tumor in adults. However, identification of the effective biomarker for the diagnosis and treatment of UVM remain to be explored. Calcium and integrin-binding protein 1 (CIB1) is emerging as an important mediator in carcinogenesis and tumor progression. In the present study, we aim to determine the contribution of CIB1 in the diagnosis of UVM.MethodsImmumohistochemical staining is used to detect the CIB1 expression level, while Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and UALCAN online tools were used to further analyze patient survival and CIB1 correlation genes in UVM. Integrative analysis using STRING and GeneMANIA predicted the correlated genes with CIB1 in UVM.ResultsTo the best of our knowledge the novel observations identified in the present study reveal that CIB1 expression level in UVM was significantly enhanced when compared with that in paracancerous tissues. A higher CIB1 expression level resulted in a significant worse disease free survival as well as overall survival. Moreover, survival probability of patients with UVM was associated with body weight and gender of the the patients. The correlated genes with CIB1 in UVM, and the similarity of the genes in UVM expression and survival heatmap was verified. Furthermore, Gene ontology enrichment analysis revealed that CIB1 and its correlated genes are significantly enriched in ITGA2B-ITGB3-CIB1 complex, regulation of intracellular protein transport and regulation of ion transport.ConclusionsTaken together, our novel findings suggested that CIB1 might be a potential diagnostic predictor for UVM, and might contribute to the potential strategy for UVM treatment by targeting CIB1.# These authors contributed equally to this work

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Copper chaperone ATOX1 is required for MAPK signaling and growth in BRAF mutation-positive melanoma

Abstract: Targeting the Cu chaperone ATOX1 in BRAFV600E-driven melanoma dampens cell growth due in part by reducing oncogenic MAPK signal transduction.

Cited by 50 publications

References 59 publications

Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis

Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis

Evaluation of copper chaperone ATOX1 as prognostic biomarker in breast cancer

CIB1 as a potential diagnosis and prognosis biomarker in uveal melanoma

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