Myc’s broad reach

Eilers, Martin; Eisenman, Robert N.

doi:10.1101/gad.1712408

Cited by 852 publications

(925 citation statements)

References 138 publications

(155 reference statements)

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“…The ability of Myc to bind to a staggeringly large number of genomic loci has also been demonstrated in ES cells [16] and is likely to underlie its activity as part of the "magic quartet" of transcription factors that can reprogram somatic cells to pluripotency [1; 17; 18; 19]. High levels of Myc may block cell differentiation and enhance self-renewal of committed and differentiated cells [20]. During tumor progression, Myc would promote the formation of cancer-initiating cells that retain developmental plasticity.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Embryonic stem cell markers expression in cancers

Schoenhals

Kassambara

Vos

et al. 2009

Biochemical and Biophysical Research Communications

223

202

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Abstract:The transcription factors Oct4 and Sox2 are highly expressed in embryonic stem (ES) cells. In conjunction with Klf4 and c-Myc, their over-expression can induce pluripotency in both mouse and human somatic cells, indicating that these factors are key regulators of the signaling network necessary for ES cell pluripotency. Self-renewal is a hallmark of stem cells and cancer and stemness program could play an important role in cancer.Therefore we compared the expression of Oct4, Sox2, Klf4 and c-Myc in 40 human tumor types to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.We found significant overexpression of at least 1/4 pluripotency factors Oct4, Sox2, Klf4 or c-Myc in 18 out of the 40 cancer types investigated. Furthermore, within a given tumor category these genes are associated with tumor progression or bad prognosis. A key goal in cancer research is to identify the mechanism by which cancer stem cells arise and self-renew. The overexpression of Oct3/4, Sox2, Klf4 and/or c-Myc could contribute to the pathologic self-renewal characteristics of cancer stem cells.

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Section: Introductionmentioning

confidence: 99%

“…A key function of Myc during normal development is to drive expansion of transit amplifying cells. Due to this unique combination of properties, oncogenic deregulation of Myc expression generates cells possessing a tumor phenotype that has no counterpart during normal development [20].…”

Section: Introductionmentioning

confidence: 99%

Embryonic stem cell markers expression in cancers

Schoenhals

Kassambara

Vos

et al. 2009

Biochemical and Biophysical Research Communications

223

202

View full text Add to dashboard Cite

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“…The transcription factor proto-oncogene Myc regulates the expression of numerous genes involved in the control of cellular metabolism, growth, and proliferation [1]. Myc is required for the maintenance of embryonic stem cells [2].…”

Section: Introductionmentioning

confidence: 99%

The Proto-Oncogene Myc Is Essential for Mammary Stem Cell Function

et al. 2012

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The mammary epithelium comprises two major cell lineages: basal and luminal. Basal cells (BCs) isolated from the mammary epithelium and transplanted into the mouse mammary fat pad cleared from the endogenous epithelium regenerate the mammary gland, strongly suggesting that the basal epithelial compartment harbors a long-lived cell population with multipotent stem cell potential. The luminal cell layer is devoid of the regenerative potential, but it contains cells with clonogenic capacity, the luminal progenitors. Mammary BCs and luminal progenitors express high levels of the transcription factor Myc. Here, we show that deletion of Myc from mammary basal epithelial cells led to impaired stem cell self-renewal as evaluated by limiting dilution and serial transplantation assays. Luminal progenitor population was significantly diminished in mutant epithelium suggesting control by the BC layer. Colony formation assay performed with isolated BCs showed that clonogenic capacity was abolished by Myc deletion. Moreover, transplanted BCs depleted of Myc failed to produce epithelial outgrowths. Stimulation with ovarian hormones estrogen (E) and progesterone (P) partially rescued the repopulation capacity of Myc-depleted BCs; however, the Myc-deficient mammary epithelium developed in response to E/P treatment lacked stem and progenitor cells. This study provides the first evidence that in the mammary gland, Myc has an essential nonredundant function in the maintenance of the self-renewing multipotent stem cell population responsible for the regenerative capacity of the mammary epithelium and is required downstream from ovarian hormones, for the control of mammary stem and progenitor cell functions.

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“…Some of the established functions of c-Myc in regulation of cell cycle progression are repression of p21Cip1 and induction of cyclin D gene transcription (Eilers and Eisenman, 2008). Furthermore, c-Myc is shown to assist oncogenic Ras in transformation and overexpression of oncogenic Ras results in c-Myc accumulation (Land et al, 1986;Sears et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

et al. 2011

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Ras is one of the most frequently activated oncogenes in cancer. Two mitogen-activated protein kinases (MAPKs) are important for ras transformation: extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase 2 (JNK2). Here we present a downstream signal amplification cascade that is critical for ras transformation in murine embryonic fibroblasts. This cascade is coordinated by ERK and JNK2 MAPKs, whose Rasmediated activation leads to the enhanced levels of three oncogenic transcription factors, namely, c-Myc, activating transcription factor 2 (ATF2) and ATF3, all of which are essential for ras transformation. Previous studies show that ERK-mediated serine 62 phosphorylation protects c-Myc from proteasomal degradation. ERK is, however, not alone sufficient to stabilize c-Myc but requires the cooperation of cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncogene that counteracts protein phosphatase 2A-mediated dephosphorylation of c-Myc. Here we show that JNK2 regulates Cip2a transcription via ATF2. ATF2 and c-Myc cooperate to activate the transcription of ATF3. Remarkably, not only ectopic JNK2, but also ectopic ATF2, CIP2A, c-Myc and ATF3 are sufficient to rescue the defective ras transformation of JNK2-deficient cells. Thus, these data identify the key signal converging point of JNK2 and ERK pathways and underline the central role of CIP2A in ras transformation.

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Myc’s broad reach

Cited by 852 publications

References 138 publications

Embryonic stem cell markers expression in cancers

Embryonic stem cell markers expression in cancers

The Proto-Oncogene Myc Is Essential for Mammary Stem Cell Function

Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

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