Mutated MITF-E87R in Melanoma Enhances Tumor Progression via S100A4

Nordlinger, Alice; Dror, Shani; Elkahloun, Abdel G.; Rio, Justine Del; Stubbs, Elisa; Golan, Tami; Malcov, Hagar; Pricket, Todd D.; Cronin, Julia C.; Parikh, Shivang; Labes, Sapir; Thomas, Luc; Yankovitz, Gal; Tabach, Yuval; Levy, Carmit; Samuels, Yardena; Khaled, Mehdi

doi:10.1016/j.jid.2018.03.1524

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…NPP uses a continuous scale of conservation instead of a defining cutoff for the protein being lost or retained and normalizes gene conservation relative to the expected conservation of other genes between the species. We applied NPP to reveal genetic interactions and novel genes in the RNA interference pathway, in RNA methylation, and in different human diseases including cancer (Schwartz et al 2013;Tabach et al 2013a,b;Sadreyev et al 2015;Findlay et al 2018;Malcov-Brog et al 2018;Nordlinger et al 2018;Omar et al 2018).…”

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confidence: 99%

Mapping global and local coevolution across 600 species to identify novel homologous recombination repair genes

et al. 2019

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The homologous recombination repair (HRR) pathway repairs DNA double-strand breaks in an error-free manner. Mutations in HRR genes can result in increased mutation rate and genomic rearrangements, and are associated with numerous genetic disorders and cancer. Despite intensive research, the HRR pathway is not yet fully mapped. Phylogenetic profiling analysis, which detects functional linkage between genes using coevolution, is a powerful approach to identify factors in many pathways. Nevertheless, phylogenetic profiling has limited predictive power when analyzing pathways with complex evolutionary dynamics such as the HRR. To map novel HRR genes systematically, we developed clade phylogenetic profiling (CladePP). CladePP detects local coevolution across hundreds of genomes and points to the evolutionary scale (e.g., mammals, vertebrates, animals, plants) at which coevolution occurred. We found that multiscale coevolution analysis is significantly more biologically relevant and sensitive to detect gene function. By using CladePP, we identified dozens of unrecognized genes that coevolved with the HRR pathway, either globally across all eukaryotes or locally in different clades. We validated eight genes in functional biological assays to have a role in DNA repair at both the cellular and organismal levels. These genes are expected to play a role in the HRR pathway and might lead to a better understanding of missing heredity in HRR-associated cancers (e.g., heredity breast and ovarian cancer). Our platform presents an innovative approach to predict gene function, identify novel factors related to different diseases and pathways, and characterize gene evolution.

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confidence: 99%

Mapping global and local coevolution across 600 species to identify novel homologous recombination repair genes

et al. 2019

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“…S100A4, S100A10, and S100A13 are associated with the OS of HNSCC, and S100A13 is correlated with DFS, according to our analysis. S100A4, also known as metastasin, plays an important role in the invasion and metastasis of human malignant tumors and is considered an EMT marker for being a direct target of β-catenin/T-cell factor (TCF) (46)(47)(48)(49). S100A10 upregulation has been reported in a number of cancers and is generally associated with a poor prognosis (50,51).…”

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confidence: 99%

An integrated bioinformatics analysis of the S100 in head and neck squamous cell carcinoma

Guo¹,

Yue²,

You³

et al. 2023

Transl Cancer Res

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Background: This study aims to evaluate the expression profile and clinical value of the S100 family in head and neck squamous cell carcinoma (HNSCC). Methods:The expression patterns, clinicopathological features, prognostic significance and underlying correlations of S100 family genes in HNSCC were determined by bioinformatics analysis with the application of several databases, including the The Cancer Genome Atlas (TCGA) and Oncomine for differential expression gene (DEG) analysis, and a series of analysis tools, including Database for Annotation, Visualization and Integrated Discovery (DAVID), cBioPortal, Kaplan-Meier Plotter, Tumor Immune Estimation Resource (TIMER) and R software packages. Results:The results from the study demonstrated that S100A4, S100A10, and S100A13 may act as prognostic markers through overall survival (OS), disease-free survival (DFS) and tumor infiltrating immune cell enrichment and a prognostic S100 family gene model comprising S100A1-A4, S100A8, S100A10, S100A12, and S100A13 was identified. The messenger RNA (mRNA) expression of S100A1, S100A9, S100A14, and S100A7A was significantly different in HNSCC patients, together with a high mutation rate of the S100 family was found. Evaluation of clinicopathological value demonstrated the heterogeneity of S100 family functions. S100A1, S100A7, S100A8, S100A9, S100A13, S100A14, and S100A16 were observed to significantly correlate with multiple biological processes (BPs) of HNSCC, including initiation, lymph node metastasis, and lymphovascular invasion. In addition, the S100 family were significantly associated with epithelial-mesenchymal transition (EMT)-related genes.Conclusions: This present study demonstrated that S100 family members are implicated in the initiation, progression, metastasis and survival of HNSCC.

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“…Other clinical studies revealed its predictive function in melanoma patients with BRAF inhibitor or CTLA-4 inhibitor treatment [137,138]. Nordlinger et al proved that poor patient prognoses are correlated with high S100A4 expression levels [139]. In addition, high serum levels of heterodimer S100A8/S100A9 in early stages of melanoma patients with ipilimumab treatment predict worse response [1].…”

Section: S100 Protein Family In Melanoma Predictionmentioning

confidence: 99%

The Role of Calcium Signaling in Melanoma

Zhang

Chen

Zhang

et al. 2022

IJMS

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Calcium signaling plays important roles in physiological and pathological conditions, including cutaneous melanoma, the most lethal type of skin cancer. Intracellular calcium concentration ([Ca2+]i), cell membrane calcium channels, calcium related proteins (S100 family, E-cadherin, and calpain), and Wnt/Ca2+ pathways are related to melanogenesis and melanoma tumorigenesis and progression. Calcium signaling influences the melanoma microenvironment, including immune cells, extracellular matrix (ECM), the vascular network, and chemical and physical surroundings. Other ionic channels, such as sodium and potassium channels, are engaged in calcium-mediated pathways in melanoma. Calcium signaling serves as a promising pharmacological target in melanoma treatment, and its dysregulation might serve as a marker for melanoma prediction. We documented calcium-dependent endoplasmic reticulum (ER) stress and mitochondria dysfunction, by targeting calcium channels and influencing [Ca2+]i and calcium homeostasis, and attenuated drug resistance in melanoma management.

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Mutated MITF-E87R in Melanoma Enhances Tumor Progression via S100A4

Cited by 8 publications

References 34 publications

Mapping global and local coevolution across 600 species to identify novel homologous recombination repair genes

Mapping global and local coevolution across 600 species to identify novel homologous recombination repair genes

An integrated bioinformatics analysis of the S100 in head and neck squamous cell carcinoma

The Role of Calcium Signaling in Melanoma

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