The complexity of the serine glycine one-carbon pathway in cancer

Reina-Campos, Miguel; Diaz-Meco, Marı́a T.; Moscat, Jorge

doi:10.1083/jcb.201907022

Cited by 90 publications

(86 citation statements)

References 162 publications

(258 reference statements)

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“…Serine hydroxymethyltransferase 2 (SHMT2), a mitochondrial SHMT, can reversibly and simultaneously catalyze the conversions of L-serine to glycine, playing significant roles in cellular one-carbon pathways [13,14]. An adequate supply of glycine is strongly responsible for rapidly proliferating cancer cells, and glycine consumption and catabolism contribute to the carcinogenesis and malignancy [15,16]. Silencing of SHMT2 is shown to be a key target for therapeutic intervention of cancer.…”

Section: Introductionmentioning

confidence: 99%

Circ_0072995 promotes cell carcinogenesis via up-regulating miR-149-5p-mediated SHMT2 in breast cancer

Qin

Zhou

et al. 2020

Preprint

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Background Circ_0072995 is a novel identified circRNA and has been identified to involve in the metastasis of breast cancer. However, the detailed function and mechanism of circ_0072995 in the biological property of breast cancer cell remain vague. Methods The expression of circ_0072995, microRNA (miR)-149-5p and serine hydroxymethyltransferase 2 (SHMT2) mRNA was detected using quantitative real-time polymerase chain reaction. Western blot was used to detect levels of SHMT2, hexokinase-2 (HK-2), lactate dehydrogenase a chain (LDHA), glucose transporter 1 (GLUT1) and phosphoinositide 3-kinase (PI3K)/p-protein kinase B (AKT) pathway/mammalian target of rapamycin (mTOR) pathway-related protein. Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity analysis, cell adhesion assay and transwell assay, respectively. Glucose metabolism was calculated by measuring glucose uptake, lactate production, and adenosine triphosphate (ATP) levels. The interaction between miR-149-5p and circ_0072995 or SHMT2 was confirmed by dual-luciferase reporter assay. In vivo tumorigenesis was performed using the murine xenograft model. Results Circ_0072995 and SHMT2 were up-regulated in breast cancer tissues and cell lines, and knockdown of circ_0072995 or SHMT2 suppressed cell malignant properties and anaerobic glycolysis; importantly, SHMT2 overexpression attenuated the anticancer action of si-Circ_0072995 in breast cancer. Besides, we also found miR-149-5p directly bound to circ_0072995 or SHMT2 in breast cancer cells, and circ_0072995 promoted the expression of SHMT2 by competitively binding to miR-149-5p. Moreover, circ_0072995 activated PI3K/AKT/mTOR pathway via elevating SHMT2 through miR-149-5p in vitro and in vivo. Additionally, xenograft tumors analysis showed circ_0072995 silence suppressed tumor growth via regulating SHMT2 and miR-149-5p. Conclusion This study demonstrated that circ_0072995 promoted cell malignant phenotypes and anaerobic glycolysis in breast cancer via up-regulating SHMT2 through sponging miR-149-5p, and activated PI3K/AKT/mTOR pathway via miR-149-5p/ SHMT2 axis, indicating a promising molecular target for breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Circ_0072995 promotes cell carcinogenesis via up-regulating miR-149-5p-mediated SHMT2 in breast cancer

Qin

Zhou

et al. 2020

Preprint

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“…Currently, other studies targeting the downstream of SSP/one-carbon metabolism are attempting to regulate the epigenetic state of the tumors and regulate the metabolic enzymes that are overactivated in the tumors (15,72,143). Epigenetic reprogramming through the regulation of the methylation pathway is essential for the malignant tumor phenotype with studies suggesting that the control of methylation is possible (144,145).…”

Section: Cancer Treatment and Potential New Opportunitiesmentioning

confidence: 99%

Serine, glycine and one‑carbon metabolism in cancer (Review)

et al. 2020

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“…Aided by modern genomics and metabolomics tools, the roles of de novo serine synthesis and mitochondrial FOCM pathway in cancer have increasingly been appreciated ( 16 , 87 , 88 ). Given the increased requirement for nucleotides to support rapid proliferation of cancer cells, metabolism of one-carbon sources, serine and glycine, and mitochondrial folate metabolic enzymes are upregulated.…”

Section: Intracellular Compartmentalization Of One-carbon Metabolismmentioning

confidence: 99%

The Roles of Mitochondrial Folate Metabolism in Supporting Mitochondrial DNA Synthesis, Oxidative Phosphorylation, and Cellular Function

Xiu

Field

2020

Current Developments in Nutrition

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Folate-mediated one-carbon metabolism (FOCM) is compartmentalized within human cells to the cytosol, nucleus, and mitochondria. The recent identifications of mitochondria-specific, folate-dependent thymidylate (dTMP) synthesis together with discoveries indicating the critical role of mitochondrial FOCM in cancer progression has renewed interest in understanding this metabolic pathway. The goal of this narrative review is to summarize recent advances in the field of one-carbon metabolism, with an emphasis on the biological importance of mitochondrial FOCM in maintaining mitochondrial DNA (mtDNA) integrity and mitochondrial function, as well as the reprogramming of mitochondrial FOCM in cancer. Elucidation of the roles and regulation of mitochondrial FOCM will contribute to a better understanding of the mechanisms underlying folate-associated pathologies.

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The complexity of the serine glycine one-carbon pathway in cancer

Cited by 90 publications

References 162 publications

Circ_0072995 promotes cell carcinogenesis via up-regulating miR-149-5p-mediated SHMT2 in breast cancer

Circ_0072995 promotes cell carcinogenesis via up-regulating miR-149-5p-mediated SHMT2 in breast cancer

Serine, glycine and one‑carbon metabolism in cancer (Review)

The Roles of Mitochondrial Folate Metabolism in Supporting Mitochondrial DNA Synthesis, Oxidative Phosphorylation, and Cellular Function

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