NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn

Guo, Shuang; Ran, Haowen; Xiao, Dake; Huang, Haohao; Mi, Lanjuan; Wang, Xinzheng; Chen, Li-Shu; Li, Da; Zhang, Songyang; Han, Qin; Zhou, Tao; Li, Ailing; Man, Jianghong

doi:10.1016/j.canlet.2019.04.003

Cited by 36 publications

(34 citation statements)

References 37 publications

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“…FYN is also highly expressed in tamoxifen-resistant estrogen receptor-positive (ER + ) breast cancer cell lines mainly because it plays an important role in the activation of important cell-cycle-associated proteins such as 14-3-3 and Cdc25A, ultimately contributing to overcoming the antiproliferative effects of tamoxifen 17 , 24 . FYN is highly associated with the growth and migration of glioma cell lines 25 , 26 . Furthermore, recent evidence has shown that FYN plays a critical role in the metastatic ability of basal-type breast cancer cells via the STAT5/NOTCH2 signaling axis 27 .…”

Section: Discussionmentioning

confidence: 99%

FYN is required for ARHGEF16 to promote proliferation and migration in colon cancer cells

Chen

et al. 2020

Cell Death Dis

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ARHGEF16 is a recently identified Rho-family guanine nucleotide exchange factor (GEF) that has been implicated in the activation of Rho-family GTPases such as Rho G, Rac, and Cdc42. However, its functions in colon cancer cell proliferation and migration are not well understood. In this study, we showed that ARHGEF16 was highly expressed in clinical specimens of colon cancer. In colon cancer cells, ARHGEF16-stimulated proliferation and migration in vitro and in vivo. Furthermore, we identified a nonreceptor tyrosine kinase, FYN, as a novel partner of ARHGEF16. Knocking down FYN expression decreased ARHGEF16 protein level in colon cancer cells. We further demonstrated that ARHGEF16-induced colon cancer cell proliferation and migration were dependent on FYN since knockdown FYN abolished the ARHGEF16-induced proliferation and migration of colon cancer cells. The FYN-ARHGEF16 axis mediates colon cancer progression and is a potential therapeutic target for colon cancer treatment.

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Section: Discussionmentioning

confidence: 99%

FYN is required for ARHGEF16 to promote proliferation and migration in colon cancer cells

Chen

et al. 2020

Cell Death Dis

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“…It has been shown that transforming growth factor-β-induced EMT may also induce a stemness phenotype in HCC cell-lines ( 43 ). In glioma stem-like cells, NT5DC2 was revealed to be highly expressed and induce the upregulation of Fyn, resulting in an aggressive phenotype ( 10 ). Moreover, in the current study, the cancer stem cell-related dataset, YAMASHITA_LIVER_CANCER_STEM_CELL_DN_96, was enriched in association with NT5DC2 expression, as assessed using GSEA.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, there have been studies on the mechanism of 5'-nucleotidase domain containing 2 (NT5DC2) in some malignancies, including gliomas (10) and liver cancer types (11). NT5DC2 has been reported to be associated with certain types of mental disorders, including schizophrenia, attention deficit hyperactivity disorder (12,13) and borderline personality disorders (14).…”

Section: Introductionmentioning

confidence: 99%

“…NT5DC2 has been reported to be associated with certain types of mental disorders, including schizophrenia, attention deficit hyperactivity disorder (12,13) and borderline personality disorders (14). NT5DC2 promotes tumorigenesis of glioma stem-like cells by inducing the expression of FYN proto-oncogene (Fyn) (10), as well as increases tumor cell proliferation in HCC by stabilizing epidermal growth factor receptor (11). Currently, to the best of our knowledge, there is no research focusing on the value of NT5DC2 in the prognosis of HCC.…”

Section: Introductionmentioning

confidence: 99%

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<em>NT5DC2</em> is a novel prognostic marker in human hepatocellular carcinoma

et al. 2020

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“…From our application of sMiST to CRC GWAS data, we identified three novel genes contributing to CRC risk that were not previously identified in the single variant analysis of the same dataset. NT5DC2 has been shown to markedly reduce the expression of Fyn, a Src family proto-oncogene and has been implicated in glioblastoma [24], though not yet linked to CRC susceptibility. Of interest there are a couple of other nearby genes in the region, NISCH and SEMA3G, which share gene-linked regulatory elements, are expressed in T cells, and have been shown to play a role in CRC [25,26].…”

Section: Plos Geneticsmentioning

confidence: 99%

A general framework for functionally informed set-based analysis: Application to a large-scale colorectal cancer study

Dong

Barfield

et al. 2020

PLoS Genet

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Genome-wide association studies (GWAS) have successfully identified tens of thousands of genetic variants associated with various phenotypes, but together they explain only a fraction of heritability, suggesting many variants have yet to be discovered. Recently it has been recognized that incorporating functional information of genetic variants can improve power for identifying novel loci. For example, S-PrediXcan and TWAS tested the association of predicted gene expression with phenotypes based on GWAS summary statistics by leveraging the information on genetic regulation of gene expression and found many novel loci. However, as genetic variants may have effects on more than one gene and through different mechanisms, these methods likely only capture part of the total effects of these variants. In this paper, we propose a summary statistics-based mixed effects score test (sMiST) that tests for the total effect of both the effect of the mediator by imputing genetically predicted gene expression, like S-PrediXcan and TWAS, and the direct effects of individual variants. It allows for multiple functional annotations and multiple genetically predicted mediators. It can also perform conditional association analysis while adjusting for other genetic variants (e.g., known loci for the phenotype). Extensive simulation and real data analyses demonstrate that sMiST yields p-values that agree well with those obtained from individual level data but with substantively improved computational speed. Importantly, a broad application of sMiST to GWAS is possible, as only summary statistics of genetic variant associations are required. We apply sMiST to a large-scale GWAS of colorectal cancer using summary statistics from �120, 000 study participants and gene expression data from a1111111111 a1111111111 a1111111111 a1111111111 a1111111111

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NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn

Cited by 36 publications

References 37 publications

FYN is required for ARHGEF16 to promote proliferation and migration in colon cancer cells

FYN is required for ARHGEF16 to promote proliferation and migration in colon cancer cells

<em>NT5DC2</em> is a novel prognostic marker in human hepatocellular carcinoma

A general framework for functionally informed set-based analysis: Application to a large-scale colorectal cancer study

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