More Than a Metabolic Enzyme: MTHFD2 as a Novel Target for Anticancer Therapy?

Zhu, Zhiyuan; Leung, Gilberto Ka Kit

doi:10.3389/fonc.2020.00658

Cited by 64 publications

(68 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aryal et al reported that glutamyl prolyl tRNA synthetase (EPRS) was selectively carbonylated in tumor breast tissue compared to normal breast tissue (31). MTHFD2, a metabolic enzyme involved in mitochondrial one-carbon folate metabolism and the high expression of MTHFD2 is associated with poor survival in breast cancer patients (32). As for NME3, Flentie et al suggested that the high expression level of NME3 increased overall survival of patients with breast cancer (33).…”

Section: Discussionmentioning

confidence: 99%

A systematic analysis of a potential metabolism-related prognostic signature for breast cancer patients

Yu¹,

Wang²,

Zhu³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

Background: Metabolic pathways play an essential role in breast cancer. However, the role of metabolismrelated genes in the early diagnosis of breast cancer remains unknown.Methods: In our study, RNA sequencing (RNA-seq) expression data and clinicopathological information from The Cancer Genome Atlas (TCGA) and GSE20685 were obtained. Univariate cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed on the differentially expressed metabolism-related genes. Then, the formula of the metabolism-related risk model was composed, and the risk score of each patient was calculated. The breast cancer patients were divided into high-risk and low-risk groups with a cutoff of the median expression value of the risk score, and the prognostic analysis was also used to analyze the survival time between these two groups. In the end, we also analyzed the expression, interaction, and correlation among genes in the metabolism-related gene risk model. Results:The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group in both TCGA and GSE20685 datasets. In addition, after adjusting for different clinicopathological features in multivariate analysis, the metabolism-related risk model remained an independent prognostic indicator in TCGA dataset. Conclusions:In summary, we systematically developed a potential metabolism-related gene risk model for predicting prognosis in breast cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

A systematic analysis of a potential metabolism-related prognostic signature for breast cancer patients

Yu¹,

Wang²,

Zhu³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…Mthfd2 is reported to play a role in embryonic development and pluripotent stem cells in mice [52,53]. In addition, Mthfd2 is associated with a poor prognosis in hematological and solid cancers [54]. Isg15 is involved in modulating the development of erythroid differentiation [55].…”

Section: Discussionmentioning

confidence: 99%

Proof of Gene Doping in a Mouse Model with a Human Erythropoietin Gene Transferred Using an Adenoviral Vector

Sugasawa¹,

Nakano²,

Fujita³

et al. 2021

Preprint

View full text Add to dashboard Cite

The World Anti-Doping Agency (WADA) has prohibited gene doping in the context of progress in gene therapy. In addition, there is a risk of the EPO gene being applied in gene doping among athletes. Along with this, development of a gene-doping test has been underway in worldwide. Here, we had two purposes: to develop a robust gene doping mouse model using the human EPO gene (hEPO) transferred using recombinant adenovirus (rAdV) as a vector and to develop a detection method to prove gene doping using this model. The rAdV including the hEPO gene were injected intravenously to transfer the gene to the liver. After injection, the mice developed significantly increased red blood cell counts in whole blood and increased gene expressions of hematopoietic markers in the spleen, indicating successful development of the gene doping model. Next, we detected direct and indirect proof of gene doping in whole blood DNA and RNA using qPCR assay and RNA sequencing. Proof was detected in one drop of whole blood DNA and RNA over a long period; furthermore, the overall RNA expression profiles significantly changed. Therefore, we have advanced detection of hEPO gene doping in humans.

show abstract

“…This makes MTHFD2 a potential target for CRC therapy. The first synthetic MTHFD1/2 inhibitor LY345899 has shown its anti-tumor activity in CRC [295]. Treatment of LY345899 led to reduced proliferative rate in primary CRC cells (SW480), its lymph node metastasis (SW620) and a liver metastatic derivative (SW620-LiM2), while no toxicity in the normal colon epithelial cells was observed [296].…”

Section: Targeting One-carbon Metabolismmentioning

confidence: 99%

Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy

Nenkov

Gaßler

et al. 2021

IJMS

View full text Add to dashboard Cite

Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a hallmark of cancer, is closely related to the initiation and progression of carcinomas, including CRC. Accumulating evidence shows that activation of oncogenic pathways and loss of tumor suppressor genes regulate the metabolic reprogramming that is mainly involved in glycolysis, glutaminolysis, one-carbon metabolism and lipid metabolism. The abnormal metabolic program provides tumor cells with abundant energy, nutrients and redox requirements to support their malignant growth and metastasis, which is accompanied by impaired metabolic flexibility in the tumor microenvironment (TME) and dysbiosis of the gut microbiota. The metabolic crosstalk between the tumor cells, the components of the TME and the intestinal microbiota further facilitates CRC cell proliferation, invasion and metastasis and leads to therapy resistance. Hence, to target the dysregulated tumor metabolism, the TME and the gut microbiota, novel preventive and therapeutic applications are required. In this review, the dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed. Possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota, are discussed.

show abstract

More Than a Metabolic Enzyme: MTHFD2 as a Novel Target for Anticancer Therapy?

Cited by 64 publications

References 57 publications

A systematic analysis of a potential metabolism-related prognostic signature for breast cancer patients

A systematic analysis of a potential metabolism-related prognostic signature for breast cancer patients

Proof of Gene Doping in a Mouse Model with a Human Erythropoietin Gene Transferred Using an Adenoviral Vector

Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy

Contact Info

Product

Resources

About