Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal

Kanatsu-Shinohara, Mito; Tanaka, Takashi; Ogonuki, Narumi; Ogura, Atsuo; Morimoto, Hiroko; Cheng, Pei Feng; Eisenman, Robert N.; Trumpp, Andreas; Shinohara, Takashi

doi:10.1101/gad.287045.116

Cited by 78 publications

(101 citation statements)

References 55 publications

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“…SC-TFs used here include CTNNB1 ( β -catenin), FOXM1, FOXO3, GLI2, HIF1A, HMGA1B, KLF4, MAF (c-MAF), MCM2, NANOG, POU5F1 (Oct-3/4), PRDM14, SNAI1 (Snail), SOX2, SOX9, STAT3, WWTR1, TBX3, TWIST1, ZEB1, LIN28A, LIN28B, and MYC (c-Myc) [18–30]. …”

Section: Methodsmentioning

confidence: 99%

Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

Yang

Zhao

Cui

et al. 2017

Stem Cells International

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Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with poor prognosis and is enriched in cancer stem cells (CSCs). However, it is not completely understood how the CSCs were maintained in TNBC. In this study, by analyzing The Cancer Genome Atlas (TCGA) provisional datasets and several small-size breast datasets, we found that cadherins (CDHs) 2, 4, 6, and 17 were frequently amplified/overexpressed in 47% of TNBC while E-cadherin (CDH1) was downregulated/mutated at 10%. The alterations of CDH2/4/6/17 were strongly associated with the elevated levels of several stem cell-related transcription factors (SC-TFs) including FOXM1, MCM2, WWTR1, SNAI1, and SOX9. CDH2/4/6/17-enriched genes including FOXM1 and MCM2 were also clustered and regulated by NFY (nuclear transcription factor Y) and/or EVI1/MECOM. Meanwhile, these SC-TFs including NFYA were upregulated in TNBC cells, but they were downregulated in luminal type of cells. Furthermore, small compounds might be predicted via the Connectivity Map analysis to target TNBC with the alterations of CDH2/4/6/17 and SC-TFs. Together with the important role of these SC-TFs in the stem cell regulation, our data provide novel insights into the maintenance of CSCs in TNBC and the discovery of these SC-TFs associated with the alterations of CDH2/4/6/17 has an implication in targeted therapy of TNBC.

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Section: Methodsmentioning

confidence: 99%

Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

Yang

Zhao

Cui

et al. 2017

Stem Cells International

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“…Several studies reveal that stemness and proliferation are closely associated with c-Myc signaling. 50,51 Herein melatonin reduced the sizes and numbers of spheres in X02 cells, while overexpression of c-Myc increased the sizes and numbers of spheres in X02 cells transfected with c-Myc overexpression plasmid ( Figure 4A). Consistently, melatonin reduced the expression of c-Myc in a concentration-dependent fashion at protein ( Figure 4B).…”

Section: Melatonin Attenuates the Expression Of C-myc And Histone Tmentioning

confidence: 98%

Melatonin disturbs SUMOylation‐mediated crosstalk between c‐Myc and nestin via MT1 activation and promotes the sensitivity of paclitaxel in brain cancer stem cells

Lee

Jung

Shin

et al. 2018

Journal of Pineal Research

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Here the underlying antitumor mechanism of melatonin and its potency as a sensitizer of paclitaxel was investigated in X02 cancer stem cells. Melatonin suppressed sphere formation and induced G2/M arrest in X02 cells expressing nestin, CD133, CXCR4, and SOX-2 as biomarkers of stemness. Furthermore, melatonin reduced the expression of CDK2, CDK4, cyclin D1, cyclin E, and c-Myc and upregulated cyclin B1 in X02 cells. Notably, genes of c-Myc related mRNAs were differentially expressed in melatonin-treated X02 cells by microarray analysis. Consistently, melatonin reduced the expression of c-Myc at mRNA and protein levels, which was blocked by MG132. Of note, overexpression of c-Myc increased the expression of nestin, while overexpression of nestin enhanced c-Myc through crosstalk despite different locations, nucleus, and cytoplasm. Interestingly, melatonin attenuated small ubiquitin-related modifier-1 (SUMO-1) more than SUMO-2 or SUMO-3 and disturbed nuclear translocation of nestin for direct binding to c-Myc by SUMOylation of SUMO-1 protein by immunofluorescence and immunoprecipitation. Also, melatonin reduced trimethylated histone H3K4me3 and H3K36me3 more than dimethylation in X02 cells by Western blotting and chromatin immunoprecipitation assay. Notably, melatonin upregulated MT1, not MT2, in X02 cells and melatonin receptor inhibitor luzindole blocked the ability of melatonin to decrease the expression of nestin, p-c-Myc(S62), and c-Myc. Furthermore, melatonin promoted cytotoxicity, sub-G1 accumulation, and apoptotic body formation by Paclitaxcel in X02 cells. Taken together, these findings suggest that melatonin inhibits stemness via suppression of c-Myc, nestin, and histone methylation via MT1 activation and promotes anticancer effect of Paclitaxcel in brain cancer stem cells.

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“…manuscript in preparation). While MYC is known to be critical in both spermatogenesis [112] and T cell activation [30], it is unclear whether MLXIP-MLX are acting cooperatively with MYC-MAX in the manner described above for MYC-driven neuroblastoma and other tumor types [107]. Moreover in a triple negative breast cancer (TNBC) cell line, and in BRAF mutant melanomas, MYC and MLXIP appear to have opposing activities, at least with regards to inducing expression of the TXNIP target gene which encodes a negative regulator of glucose transport [113,114].…”

Section: Involvement Of Mlxip-mlx In the Response To Cellular Stressmentioning

confidence: 99%

The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

et al. 2018

Self Cite

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Transcription factor networks have evolved in order to control, coordinate, and separate, the functions of distinct network modules spatially and temporally. In this review we focus on the MYC network (also known as the MAX-MLX Network), a highly conserved super-family of related basic-helix-loop-helix-zipper (bHLHZ) proteins that functions to integrate extracellular and intracellular signals and modulate global gene expression. Importantly the MYC network has been shown to be deeply involved in a broad spectrum of human and other animal cancers. Here we summarize molecular and biological properties of the network modules with emphasis on functional interactions among network members. We suggest that these network interactions serve to modulate growth and metabolism at the transcriptional level in order to balance nutrient demand with supply, to maintain growth homeostasis, and to influence cell fate. Moreover, oncogenic activation of MYC and/or loss of a MYC antagonist, results in an imbalance in the activity of the network as a whole, leading to tumor initiation, progression and maintenance.

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Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal

Cited by 78 publications

References 55 publications

Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

Melatonin disturbs SUMOylation‐mediated crosstalk between c‐Myc and nestin via MT1 activation and promotes the sensitivity of paclitaxel in brain cancer stem cells

The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

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