Increased Expression of SHMT2 Is Associated With Poor Prognosis and Advanced Pathological Grade in Oral Squamous Cell Carcinoma

Wu, Zhi‐Zhong; Wang, Shuo; Yang, Qi‐Chao; Wang, Xiaolong; Yang, Leilei; Liu, Bing; Sun, Zhi‐Jun

doi:10.3389/fonc.2020.588530

Cited by 17 publications

(18 citation statements)

References 40 publications

(66 reference statements)

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“…It has been reported that SHMT2, a key metabolic enzyme, can regulate cancer cell regulation and metabolism [ 7 ]. It is noteworthy that up-regulation of SHMT2 predicts a poor prognosis of OSCC patients [ 12 ]. This study was the first to explore the function of SHMT2 in OSCC.…”

Section: Resultsmentioning

confidence: 99%

“…SHMT2 has shown prognostic and therapeutic value for many cancers, such as hepatic carcinoma, breast cancer, glioma, and thyroid cancer [ 26–29 ]. To our knowledge, SHMT2 is a key metabolic enzyme in the synthesis of glycine from serine and up-regulation of SHMT2 predicted a poor prognosis of OSCC patients [ 12 ]. However, the function of SHMT2 in OSCC is uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, EMT event, which is chiefly marked by the decrease of E-cadherin and the increase of vimentin, occupies an important position in tumor metastasis [ 4 , 44 ]. It was reported that SHMT2 affects the EMT process in OSCC by modulating the classical marker of EMT [ 12 ]. In this study, it was noted that SHMT2 deficiency also lead to prominent inhibition of invasion, metastasis, and EMT in OSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Extensive literature has demonstrated the important catalytic function of SHMT2 in various human cancers and its association with tumor growth [ 8–11 ]. Moreover, it has been mentioned that up-regulation of SHMT2 predicted a poor prognosis of OSCC patients [ 12 ]. However, the function of SHMT2 in OSCC is uncertain.…”

Section: Introductionmentioning

confidence: 99%

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Serine hydroxymethyltransferase 2 (SHMT2) potentiates the aggressive process of oral squamous cell carcinoma by binding to interleukin enhancer-binding factor 2 (ILF2)

et al. 2022

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Oral squamous cell carcinoma (OSCC) is a frequent threatening head and neck malignancy. Serine hydroxymethyltransferase 2 (SHMT2) was identified to be upregulated in OSCC and its high expression was associated with poor patient prognosis. This paper set out to assess the influence of SHMT2 on OSCC progression and the potential mechanisms related to interleukin enhancer-binding factor 2 (ILF2). First of all, reverse transcription-quantitative PCR (RT-qPCR) and western blot examined the expression of SHMT2 and ILF2 in OSCC cells. Cell Counting Kit-8 (CCK-8) and colony formation assays appraised cell proliferation. Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) staining was to estimate the apoptotic rate of cells. Further, wound healing and transwell assays verified the migration and invasion of cells. Western blot was adopted to detect the expression of factors related to apoptosis, migration, and epithelial–mesenchymal transition (EMT). The possible interaction of SHMT2 and ILF2 was predicted by a Molecular INTeraction (MINT) and BioGRID databases and determined using co-immunoprecipitation (IP) assay. Subsequently, ILF2 was overexpressed to investigate whether SHMT2 regulated OSCC progression by binding to ILF2. Results implied that SHMT2 possessed increased expression in OSCC cells, and OSCC cell viability, migration, invasion, EMT were inhibited and apoptosis was potentiated after its silencing. ILF2 bound to SHMT2 and ILF2 expression was downregulated after SHMT2 silencing in OSCC cells. Importantly, ILF2 overexpression abolished the suppressive role of SHMT2 interference in the progression of OSCC. Collectively, SHMT2 could promote the progression of OSCC by binding to ILF2.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serine hydroxymethyltransferase 2 (SHMT2) potentiates the aggressive process of oral squamous cell carcinoma by binding to interleukin enhancer-binding factor 2 (ILF2)

et al. 2022

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“…SLC3A2 could contribute to migration, invasion and proliferation and even decrease apoptosis in OSCC. Zhizhong Wu et al [ 18 ] found that serine hydroxymethyltransferase 2 (SHMT2), which serves as an independent prognostic marker, is overexpressed in OSCC, especially in advanced OSCC. SHMT2 is implicated in neoplasia and is associated with the expression of CD274 molecule (CD274), CKLF-like MARVEL transmembrane domain containing 6 (CMTM6), V-set immunoregulatory receptor (VSIR), V-set domain containing T cell activation inhibitor 1 (VTCN1), snail family transcriptional repressor 2 (SNAI2), and bone marrow stromal cell antigen 2 (BST2) in the tumor microenvironment of OSCC.…”

Section: Illustration Of Prognostic Indicators In Osccmentioning

confidence: 99%

The integration of differentially expressed genes based on multiple microarray datasets for prediction of the prognosis in oral squamous cell carcinoma

2021

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Oral squamous cell carcinoma (OSCC) is a common human malignancy. However, its pathogenesis and prognostic information are poorly elucidated. In the present study, we aimed to probe the most significant differentially expressed genes (DEGs) and their prognostic performance in OSCC. Multiple microarray datasets from the Gene Expression Omnibus (GEO) database were aggregated to identify DEGs between OSCC tissue and control tissue. Least absolute shrinkage and selection operator (LASSO) Cox model was constructed to determine the prognostic performance of the aggregated DEGs based on The Cancer Genome Atlas (TCGA) OSCC cohort. Ten datasets with 341 OSCC samples and 283 control samples were included. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that the integrated DEGs were enriched in the IL-17 signaling pathway, viral protein interactions with cytokines and cytokine receptors, and amoebiasis, among others. Our LASSO Cox model was able to discriminate two groups with different overall survival in the training cohort and test cohort (p < 0.001). The time-dependent receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) values at one year, three years, and five years were 0.831, 0.898, and 0.887, respectively. In the testing cohort, the time-dependent ROC curve showed that the AUC values at one year, three years, and five years were 0.696, 0.693, and 0.860, respectively. Our study showed that the integrated DEGs of OSCC might be applicable in the evaluation of prognosis in OSCC. However, further research should be performed to validate our findings.

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Target enzymes in serine‐glycine‐one‐carbon metabolic pathway for cancer therapy

Sun

Zhao

Cui

2022

Intl Journal of Cancer

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Cancer cells selectively take up exogenous serine or synthesize serine via the serine synthesis pathway for conversion into intracellular glycine and one-carbon units for nucleotide biosynthesis. In this process, serine-glycine metabolism and the onecarbon cycle play vital roles, which is named serine-glycine-one-carbon metabolism (SGOC). The SGOC pathway is a metabolic network crucial for tumorigenesis with unexpected complexity and clinical importance. Accumulating evidence has demonstrated that metabolic enzymes in SGOC metabolism play key roles in tumorigenesis, metastasis and resistance to therapies. In this review, we focus on the involvement of serine and glycine in the folate-mediated one-carbon pathway during cancer progression and highlight the pathways through which cancer cells acquire and use onecarbon units. In addition, we discuss the recently elucidated effects of SGOC (folate cycle) metabolic enzymes in the occurrence and development of tumors and their links to drug resistance. Inhibitors of target enzymes in the SGOC pathway display promise as investigational new drug candidates for the treatment of tumors.

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Increased Expression of SHMT2 Is Associated With Poor Prognosis and Advanced Pathological Grade in Oral Squamous Cell Carcinoma

Cited by 17 publications

References 40 publications

Serine hydroxymethyltransferase 2 (SHMT2) potentiates the aggressive process of oral squamous cell carcinoma by binding to interleukin enhancer-binding factor 2 (ILF2)

Serine hydroxymethyltransferase 2 (SHMT2) potentiates the aggressive process of oral squamous cell carcinoma by binding to interleukin enhancer-binding factor 2 (ILF2)

The integration of differentially expressed genes based on multiple microarray datasets for prediction of the prognosis in oral squamous cell carcinoma

Target enzymes in serine‐glycine‐one‐carbon metabolic pathway for cancer therapy

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