EWS‐FLI1 reprograms the metabolism of Ewing sarcoma cells via positive regulation of glutamine import and serine‐glycine biosynthesis

Sen, Nirmalya; Cross, Allison M.; Lorenzi, Philip L.; Khan, Javed; Gryder, Berkley E.; Kim, Suntae; Caplen, Natasha J.

doi:10.1002/mc.22849

Cited by 40 publications

(37 citation statements)

References 56 publications

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“…B, Tumour growth curves revealed that xenograft tumour growth in nude mice was significantly slower in shMTHFD2-treated group than that of shCtrl. [21][22][23] During the treatments of acute myeloid leukaemia and colorectal cancer, targeting MTHFD2 can markedly suppress the tumour progression both in vitro and in vivo. D, Western blot analysis of MTHFD2 in tumour xenograft tissues.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

Chang

Yang

Cai

et al. 2019

J Cellular Molecular Medi

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Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme located in the mitochondria. It has been reported to be overexpressed in several malignancies. However, the relationship between the expression of MTHFD2 and non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that MTHFD2 was significantly overexpressed in NSCLC tissues and cell lines. Knockdown of MTHFD2 resulted in reduced cell growth and tumorigenicity in vitro and in vivo. Besides, the mRNA and protein expression level of cell cycle genes, such as CCNA2, MCM7 and SKP2, was decreased in MTHFD2 knockdown H1299 cells. Our results indicate that the inhibitory effect of MTHFD2 knockdown on NSCLC may be mediated via suppressing cell cycle-related genes. These findings delineate the role of MTHFD2 in the development of NSCLC and may have potential applications in the treatment of NSCLC. K E Y W O R D S bioinformatics, cell cycle, methylenetetrahydrofolate dehydrogenase 2, non-small cell lung cancer | 1569 YU et al. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Yu C, Yang L, Cai M, et al. Downregulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes. J Cell Mol Med.

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Section: Discussionmentioning

confidence: 99%

Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

Chang

Yang

Cai

et al. 2019

J Cellular Molecular Medi

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“…3 Inhibition of PSAT1 promotes DNA damage and apoptosis. 4,5 PSAT1 increases resistance in melanoma, pancreatic, and non-small cell lung cancer cells. 6 High PSAT1 expression is found in triple-negative breast cancer and is closely associated with aggressive frequently metastasizes and clinical prognosis.…”

Section: Introductionmentioning

confidence: 99%

<p>PSAT1 Regulated Oxidation-Reduction Balance Affects the Growth and Prognosis of Epithelial Ovarian Cancer</p>

Zhang¹,

Li²,

Dong³

et al. 2020

OTT

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Introduction: A growing number of studies have found that the serine-glycine biosynthesis pathway is highly activated for biosynthesis in cancer progression and metastasis. Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second step of the serine-glycine biosynthesis pathway; the effects and mechanism of PSAT1 in epithelial ovarian cancer (EOC) remains unclear. Materials and Methods: The expression of PSAT1 in clinical EOC samples and normal ovarian tissues was conducted by RT-PCR, Western blot, and immunohistochemical staining. Survival analysis of PSAT1 in ovarian cancer was performed by using the public database. Following the downregulation of PSAT1, the cell growth, cell apoptosis, and cell cycle in ovarian cancer cells were respectively examined by the soft agar colony formation assay and flow cytometry analysis. Then the glutathione (GSH) levels, the GSH/GSSG ratio, the NADPH/NADP ratio, and the cellular reactive oxygen species (ROS) levels were tested to analyze the oxidation-reduction balance in PSAT1-depleted ovarian cancer cells. Results: PSAT1 is markedly over-expressed in clinical EOC samples (n = 90) compared to that in normal ovarian tissues (n = 10), and the expression of PSAT1 is correlated with histological subtype, FIGO stage, histological grade, lymph node metastasis, distant metastasis and the presence of ascites. Public database analysis shows that higher PSAT1 indicates poor survival in EOC patients. Downregulation of PSAT1 in EOC cells inhibits growth, induces apoptosis and cell cycle arrest in vitro. EOC cells with high PSAT1 levels have increased a higher GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio and lower reactive oxygen species (ROS) content. The cancer-killing effects of PSAT1 knockdown are reversed by exogenous glutathione. PSAT1 participates in cancer growth by regulating oxidation-reduction balance. Conclusion: Therefore, these results highlight the potential of PSAT1 inhibitors or metabolic substrate deprivation as therapeutic strategies for treating patients with EOC, especially those with advanced stages of cancer.

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“…For example, PSPH contributes to cell survival and proliferation by interacting with c‐MYC under glucose/glutamine deprivation conditions in hepatocellular carcinoma . Additionally, a high PSPH level promotes cancer cell proliferation and survival through an accumulation of reactive oxygen species and DNA damage, and facilitates brain and bone metastasis by simulating osteoclastogenesis . These findings demonstrate that PSPH may play a vital role in tumorigenesis and progression and may serve as a promising molecular target for human cancer.…”

Section: Discussionmentioning

confidence: 87%

Upregulation of phosphoserine phosphatase contributes to tumor progression and predicts poor prognosis in non‐small cell lung cancer patients

Liao

et al. 2019

Thoracic Cancer

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Background Growing evidence indicates that high phosphoserine phosphatase (PSPH) expression is associated with tumor prognosis in many types of cancers. However, the role of PSPH in non‐small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the clinical significance of PSPH in NSCLC. Methods One hundred forty‐three patients with histologically confirmed NSCLC who underwent surgery were included. Quantitative real‐time PCR and Western blot were used to assess PSPH expression in paired tumor and corresponding adjacent non‐tumorous tissues. The role of PSPH in invasion and cell growth was investigated in vitro. Results Compared to adjacent normal lung tissues, PSPH messenger RNA and protein levels were significantly higher in NSCLC tissues, and the PSPH expression level was positively related to clinical stage, metastasis, and recurrence. High PSPH expression was predictive of poor overall survival. A549 cells transfected with small interfering‐PSPH showed inhibited cell migration, invasion, and proliferation. We further demonstrated that PSPH might promote the invasive capabilities of NSCLC cells through the AKT/AMPK signaling pathway. Conclusion Our results indicate that PSPH may act as a putative oncogene in NSCLC, and may be a vital molecular marker for the metastasis and proliferation of NSCLC cells by regulating the AKT/AMPK signaling pathway.

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EWS‐FLI1 reprograms the metabolism of Ewing sarcoma cells via positive regulation of glutamine import and serine‐glycine biosynthesis

Cited by 40 publications

References 56 publications

Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

<p>PSAT1 Regulated Oxidation-Reduction Balance Affects the Growth and Prognosis of Epithelial Ovarian Cancer</p>

Upregulation of phosphoserine phosphatase contributes to tumor progression and predicts poor prognosis in non‐small cell lung cancer patients

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