Gfer inhibits Jab1-mediated degradation of p27<sup>kip1</sup>to restrict proliferation of hematopoietic stem cells

Teng, Ellen C.; Todd, Lance R.; Ribar, Thomas J.; Lento, William; DiMascio, Leah; Means, Anthony R.; Sankar, Uma

doi:10.1091/mbc.e10-08-0723

Cited by 12 publications

(28 citation statements)

References 43 publications

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“…36) or cell-cycle regulators through P27 function (GFER; refs. 37,38). Metabolic alterations in tumor cells are thought to be important for the tumor phenotype and evolution and to affect response to therapy (39).…”

Section: /Cd24mentioning

confidence: 99%

ALDH1-Positive Cancer Stem Cells Predict Engraftment of Primary Breast Tumors and Are Governed by a Common Stem Cell Program

et al. 2013

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Cancer stem-like cells (CSC) have been widely studied, but their clinical relevance has yet to be established in breast cancer. Here, we report the establishment of primary breast tumor-derived xenografts (PDX) that encompass the main diversity of human breast cancer and retain the major clinicopathologic features of primary tumors. Successful engraftment was correlated with the presence of ALDH1-positive CSCs, which predicted prognosis in patients. The xenografts we developed showed a hierarchical cell organization of breast cancer with the ALDH1-positive CSCs constituting the tumorigenic cell population. Analysis of gene expression from functionally validated CSCs yielded a breast CSC signature and identified a core transcriptional program of 19 genes shared with murine embryonic, hematopoietic, and neural stem cells. This generalized stem cell program allowed the identification of potential CSC regulators, which were related mainly to metabolic processes. Using an siRNA genetic screen designed to target the 19 genes, we validated the functional role of this stem cell program in the regulation of breast CSC biology. Our work offers a proof of the functional importance of CSCs in breast cancer, and it establishes the reliability of PDXs for use in developing personalized CSC therapies for patients with breast cancer. Cancer Res; 73(24); 7290-300. Ó2013 AACR.

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Section: /Cd24mentioning

confidence: 99%

ALDH1-Positive Cancer Stem Cells Predict Engraftment of Primary Breast Tumors and Are Governed by a Common Stem Cell Program

et al. 2013

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“…9 For example, this polymorphism falls within a region that physically interacts with the Jun activation domain-binding protein 1 ( JAB1), which triggers the proteolytic degradation of p27. 10,11 It has been speculated that the p27V109G polymorphism enhances the degradation of this variant protein, and possibly leads to cell cycle dysregulation and tumorigenesis. Recently, many studies on the relationship between the p27V109G polymorphism and cancer risk have been reported, but the results were inconsistent.…”

Section: Introductionmentioning

confidence: 99%

p27^Kip1 V109G Polymorphism and Cancer Risk: A Systematic Review and Meta-Analysis

Feng

Xu²,

Tang³

et al. 2012

Cancer Biotherapy and Radiopharmaceuticals

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Relationship between the p27Kip1 (here after referred to as p27) V109G polymorphism and cancer risk has been extensively studied; however, results from different studies were not fully consistent. Therefore, we carried out a meta-analysis to comprehensively assess the correlation between the p27V109G polymorphism and the cancer risk. Articles on the relationship of the p27V109G polymorphism with cancer risk were searched from Medline, Pub Med, and Web of science databases. A total of eight eligible studies with 3591 cases and 3799 controls were included in this meta-analysis. Overall, it seemed that the G allele was not associated with the elevated cancer risk (pooled odds ratio [OR] = 0.98, 95% confidence interval [CI]: 0.88-1.09, p = 0.68, fixed effects). Analyses in different populations revealed that no statistically significant associations between the G allele and cancer risk were demonstrated in Caucasians or Asians. When analyzed in different types of cancer that, from two studies, the G allele was found to be associated with a decreased risk of prostate cancer in a dominant genetic model (pooled OR = 0.60, 95% CI = 0.36-0.98, p = 0.04, fixed effects), but did not alter the breast cancer risk from four studies. In conclusion, this meta-analysis indicated that the p27V109G polymorphism did not correlate with the overall cancer risk in the general population.

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“…ALR was shown to be highly expressed in fetal livers [31]. Meanwhile, the ALR/Gfer gene was also enriched in many other stem cells, such as mouse embryonic stem cells (ESCs) [32,33] and neuronal and hematopoietic stem cells (HSCs) [34]. In HSCs, the high expression of Gfer could restrict the abnormal HSC proliferation through its inhibition of Jab1-mediated turnover of p27 kip1 [34].…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, the ALR/Gfer gene was also enriched in many other stem cells, such as mouse embryonic stem cells (ESCs) [32,33] and neuronal and hematopoietic stem cells (HSCs) [34]. In HSCs, the high expression of Gfer could restrict the abnormal HSC proliferation through its inhibition of Jab1-mediated turnover of p27 kip1 [34]. In ESCs, Gfer plays an essential role in the maintenance of murine ESC pluripotency by preserving the structural and functional integrity of the mitochondria based on modulation of the key mitochondrial fission factor Drp1 (dynamic-related protein 1) [35].…”

Section: Discussionmentioning

confidence: 99%

Involvement of Hepatic Stimulator Substance in the Regulation of Hepatoblast Maturation into Hepatocytes In Vitro

Sun

Liu²,

An³

2014

Stem Cells and Development

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Hepatic stimulator substance (HSS), also known as augmenter of liver regeneration (ALR), acts as a hepatotrophic growth factor to promote liver regeneration after liver damage or partial hepatectomy. However, the expression and function of HSS during liver development in mammals remain largely unknown. In this work, the hepatoblasts were isolated from mice at embryonic day 13.5 (E13.5), and HSS expression and its role during hepatoblast maturation were investigated. The results showed that HSS expression was enhanced in the hepatoblasts compared with mouse primary hepatocytes. HSS expression (23 kDa) was significantly decreased if the hepatoblast maturation was induced by a combination of oncostatin M (OSM), dexamethasone (DEX), and hepatocyte growth factor (HGF). We also found that knockdown of HSS expression (mainly 23-kDa isoform) by siRNA promoted hepatoblast maturation and also activated the signal transducer and activator of transcription 3 (STAT3) phosphorylation levels. However, if STAT3 activity was blocked by a small-molecule inhibitor Stattic, then hepatocyte maturation could be abolished, suggesting that STAT3 was most likely a potential molecule responsible for HSS signaling. In summary, our results demonstrated for the first time that HSS might be an active factor participating in the regulation of liver development and hepatocyte maturation.

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Gfer inhibits Jab1-mediated degradation of p27^kip1to restrict proliferation of hematopoietic stem cells

Cited by 12 publications

References 43 publications

ALDH1-Positive Cancer Stem Cells Predict Engraftment of Primary Breast Tumors and Are Governed by a Common Stem Cell Program

ALDH1-Positive Cancer Stem Cells Predict Engraftment of Primary Breast Tumors and Are Governed by a Common Stem Cell Program

p27^Kip1 V109G Polymorphism and Cancer Risk: A Systematic Review and Meta-Analysis

Involvement of Hepatic Stimulator Substance in the Regulation of Hepatoblast Maturation into Hepatocytes In Vitro

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Gfer inhibits Jab1-mediated degradation of p27kip1to restrict proliferation of hematopoietic stem cells

Cited by 12 publications

References 43 publications

ALDH1-Positive Cancer Stem Cells Predict Engraftment of Primary Breast Tumors and Are Governed by a Common Stem Cell Program

ALDH1-Positive Cancer Stem Cells Predict Engraftment of Primary Breast Tumors and Are Governed by a Common Stem Cell Program

p27Kip1 V109G Polymorphism and Cancer Risk: A Systematic Review and Meta-Analysis

Involvement of Hepatic Stimulator Substance in the Regulation of Hepatoblast Maturation into Hepatocytes In Vitro

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Gfer inhibits Jab1-mediated degradation of p27^kip1to restrict proliferation of hematopoietic stem cells

p27^Kip1 V109G Polymorphism and Cancer Risk: A Systematic Review and Meta-Analysis