A Myc rather than core pluripotency module accounts for the shared signatures of embryonic stem and cancer cells

By Jonghwan Kim, A. Woo, J. Chu, Jonathan W. Snow, Y. Fujiwara, C. Kim, A. Cantor, Stuart H. Orkin. Cell, 2010

673 citations recorded by the source corpus.

SUMMARY c-Myc (Myc) is an important transcriptional regulator in embryonic stem (ES) cells, somatic cell reprogramming, and cancer. Here, we identify a Myc-centered regulatory network in ES cells by combining protein-protein and protein-DNA interaction studies, and show that Myc interacts with the NuA4 complex, a regulator of ES cell identity. In combination with regulatory network information, we define three ES cell modules (Core, Polycomb, and Myc), and show that the modules are functionally separable, illustrating that the overall ES cell transcription program is comprised of distinct units. With these modules as an analytical tool, we have reassessed the hypothesis linking an ES cell signature with cancer or cancer stem cells. We find that the Myc module, independent of the Core module, is active in various cancers and predicts cancer outcome. The apparent similarity of cancer and ES cell signatures reflects in large part the pervasive nature of Myc regulatory network.

View Paper: https://www.semanticscholar.org/paper/0558c86aaf8fbd9ea10a615b6ad3c98d6b47c961

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Citations in the corpus

MYC, metabolism, cell growth, and tumorigenesis. (2013, background): “High-quality MYC-binding sites are on the order of 10,000 or more per human genome, although MYC binding does not necessarily correlate with gene expression changes, particularly in systems in which MYC is inducible (Zeller et al. 2006; Kim et al. 2010; Lee et al. 2012; Lin et al. 2012; Nie et al. 2”
Cancer stem cells in glioblastoma (2015, background): “CSC regulation converges on MYC, which occurs in the presence of MYC-mediated cancer cell survival and proliferation programs (Wang et al. 2008; Zheng et al. 2008; Wurdak et al. 2010; Chan et al. 2012; Fang et al. 2014).”
The tumorigenicity of human embryonic and induced pluripotent stem cells (2011, background): “The potential of MYC ablation for teratoma prevention seems even more promising in view of a recent report that MYC regulatory networks account for most of the transcriptional similarity between embryonic stem cells and cancer cell”
Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation (2018, background): “Those molecular features are causally connected to particular oncogenic signaling pathways that regulate transcriptional networks that sustain the growth and proliferation of cancer cells (Ben-Porath et al., 2008; Eppert et al., 2011; Kim et al., 2010).”
Senescence impairs successful reprogramming to pluripotent stem cells. (2009, background): “Myc genes rather than core pluripotency module genes (Kim et al., 2010).”
MYC on the Path to Cancer (2012, background): “Could MYC or Myc’s target genes be targeted for cancer therapy?”
Myc and cell cycle control. (2015, background): “CCND1 (cyclin D1) Induced Rodent fibroblasts [142–144] ChIP-on-ChIP/mouse ES cells [107]”
Control of Embryonic Stem Cell State (2011, background): “…of the ESC gene expression program are recapitulated in cancer cells (Ben-Porath et al., 2008), and it has been argued that this is largely a consequence of c-Myc (Kim et al., 2010a). c-Myc amplification is the most frequent somatic copy-number amplification in tumor cells (Beroukhim et al., 2010).”
The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. (2011, background): “Yet, the correlation of ESC genes with cancer progression has been recently undermined by the finding that a Myc-driven gene program rather than core pluripotency genes accounts for similarities between ESCs and cancer stem cells (Kim et al., 2010).”