ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4

Kim, Myoung Ok; Kim, Sung Hyun; Cho, Yong‐Yeon; Nadas, Janos; Jeong, Chul Ho; Yao, Ke; Kim, Dong Joon; Yu, Dong Hoon; Keum, Young‐Soo; Lee, Kun Yeong; Huang, Zunnan; Bode, Ann M.; Dong, Zigang

doi:10.1038/nsmb.2217

Cited by 150 publications

(150 citation statements)

References 46 publications

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“…The oncogenic effect of KLF4 has been reported in breast and squamous cell carcinoma [243][244][245][246][247], while its tumor suppression role was reported in various types of cancers such as colon cancer [248,249]. It was demonstrated that KLF4 is a fast turnover protein, whose turnover-half life is governed by the ubiquitin-proteasome system [250,251]. Several e3 ligases such as APC/CDH1 and CUL2/vHL have been linked to the turnover of KLF4 in response to different signaling [224,252].…”

Section: Crosstalk With Tgf-β Signalingmentioning

confidence: 99%

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Zhou

Qiao

Shetty

et al. 2013

Cell. Mol. Life Sci.

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Estrogen and estrogen receptors (ERs) are critical regulators of breast epithelial cell proliferation, differentiation, and apoptosis. Compromised signaling vis-à-vis the estrogen receptor is believed © Springer Basel 2013 yow4@pitt.edu. ), which predicts for response to endocrine-based therapy; however, innate or acquired resistance to endocrinebased drugs remains a serious challenge. The complexity of regulation for estrogen signaling coupled with the crosstalk of other oncogenic signaling pathways is a reason for endocrine therapy resistance. Alternative strategies that target novel molecular mechanisms are necessary to overcome this current and urgent gap in therapy. A thorough analysis of estrogen-signaling regulation is critical. In this review article, we will summarize current insights into the regulation of estrogen signaling as related to breast carcinogenesis and breast cancer therapy. NIH Public Access

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Section: Crosstalk With Tgf-β Signalingmentioning

confidence: 99%

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Zhou

Qiao

Shetty

et al. 2013

Cell. Mol. Life Sci.

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“…It remains poorly understood which molecular mechanisms link Erk to the pluripotency network, but some progress has been made recently. Two pluripotency factors, Klf2 and Klf4 have been shown to be directly phosphorylated by Erk, which promotes their degradation [22,23]. Klf4 in turn induces the E3 ubiquitin ligase March5, which promotes the pluripotent state by inhibiting the Mek/Erk cascade [14].…”

Section: The Pluripotency-associated Signalling Networkmentioning

confidence: 99%

“…The central pluripotencydestabilizing pathway is the MAPK pathway, stimulated by Fgf4, which is expressed in an autocrine fashion by the ES cells themselves. Through the activation of Mek and Erk, Fgf4 leads to the downregulation of Nanog at the transcriptional level, but also destabilizes Klf2 and Klf4 protein through Erk-dependent phosphorylation [22,23]. Moreover, Gsk3, which can mediate Wnt signalling has a differentiation promoting effect by repressing several pluripotency factors, [14], c [15], d [16], e [17], f [18], g [19], h [20], i [21], j [22], k [23], l [24], m [25], n [26], o [27].…”

Section: Sex Differences In Murine Embryonic Stem Cellsmentioning

confidence: 99%

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

Schulz

2017

Phil. Trans. R. Soc. B

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Already during early embryogenesis, before sex-specific hormone production is initiated, sex differences in embryonic development have been observed in several mammalian species. Typically, female embryos develop more slowly than their male siblings. A similar phenotype has recently been described in differentiating murine embryonic stem cells, where a double dose of the X-chromosome halts differentiation until dosage-compensation has been achieved through X-chromosome inactivation. On the molecular level, several processes associated with early differentiation of embryonic stem cells have been found to be affected by X-chromosome dosage, such as the transcriptional state of the pluripotency network, the activity pattern of several signal transduction pathways and global levels of DNA-methylation. This review provides an overview of the sex differences described in embryonic stem cells from mice and discusses a series of X-linked genes that are associated with pluripotency, signalling and differentiation and their potential involvement in mediating the observed X-dosage–dependent effects. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

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“…Therefore these factors may cooperatively maintain the CSC phenotype, perhaps by regulating the self-renewal and pluripotency of embryonic stem cells (30,31). The experimental system described in the present study may inform future xperiments to test directly whether and how these genes are involved in the CSC-like phenotype of SP cells in HCC.…”

Section: Discussionmentioning

confidence: 99%

Side population in hepatocellular carcinoma HCCLM3 cells is enriched with stem-like cancer cells

et al. 2016

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Abstract. Substantial evidence implicates that low-abundance cancer stem cells (CSCs) are responsible for tumor metastasis and recurrence in hepatocellular carcinoma (HCC). Side population (SP) cells possess typical CSCs-like features, and are frequently considered as a special subpopulation in which CSCs are enriched and in studies may be considered as a substitute for CSCs. The aim of the present study was to examine the abundance of SP cells in human HCC cell lines with different metastatic potentials and compare their CSC-like, tumorigenic and invasive properties with those of the main population (MP) cells. An experimental system is described for identifying SP cells and analyzing their CSC-like properties. The relative abundance of SP cells correlated directly with the metastatic potential of the HCC cell line: HCCLM3, 16.3±2.2%; MHCC97-H, 8.4±0.7%; MHCC97-L, 4.7±0.5%; and Huh7, 1.0±0.3% (P<0.05). SP cells isolated from HCCLM3 cultures showed significantly higher proliferation rates and clonogenicity than the corresponding MP cells, in addition to higher migration and invasive abilities in vitro and greater tumorigenicity in mice. Expression levels of all CSC-associated genes tested, except EpCAM and Oct4, were significantly higher in SP cells. The findings revealed that the proportion of SP cells correlates with metastatic potential, and SP cells demonstrated the characteristics expected of CSCs, implicating them in HCC metastasis. Further studies on the identification and characterization of SP cells using clinical HCC specimens will contribute to the understanding of how SP cells are involved in these disease processes.

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ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4

Cited by 150 publications

References 46 publications

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

Side population in hepatocellular carcinoma HCCLM3 cells is enriched with stem-like cancer cells

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