SHMT2 Induces Stemness and Progression of Head and Neck Cancer

Jin, Yanli; Jung, Seung-Hyun; Lim, Mi Ae; Oh, Chahyun; Piao, Yudan; Kim, Hae Jong; Nguyena, QuocKhanh; Kang, Yea Eun; Chang, Jae Won; Won, Ho-Ryun; Koo, Bon Seok

doi:10.3390/ijms23179714

Cited by 8 publications

(3 citation statements)

References 45 publications

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“…On the other hand, the expression level of SHMT2 in BLCA was significantly higher compared to normal bladder tissue (* P < 0.05, *** P < 0.001), and BLCA patients with high SHMT2 expression had significantly lower clinical survival time. Similar findings have been reported in studies on head and neck cancer and colorectal cancer samples from the TCGA database 30 . Therefore, among the two serine hydroxymethyltransferase isozymes, only SHMT2 shows a significant difference in expression between BLCA and normal tissues, suggesting its involvement in the biological progression of BLCA.…”

Section: Discussionsupporting

confidence: 90%

A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer

Su,

Chen,

Wang

et al. 2024

Sci Rep

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Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

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Section: Discussionsupporting

confidence: 90%

A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer

Su,

Chen,

Wang

et al. 2024

Sci Rep

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“…Recent studies have shown that overexpression of SHMT2 is observed in a variety of cancers, including breast, melanoma, lung, ovarian, and prostate cancers (Anderson et al 2011 ; Ding et al 2013 ; Lee et al 2014 ), and that it is associated with tumorigenesis and progression. SHMT2 has been shown in clinical studies that the higher the expression, the more aggressive the tumor is and the worse the prognosis (Jin et al 2022 ). Therefore, SHMT2 is an important potential target for metabolic reprogramming in tumors and its role in tumors needs to be further explored.…”

Section: Introductionmentioning

confidence: 99%

Construction and validation of a folate metabolism-related gene signature for predicting prognosis in HNSCC

Wang,

He,

Bai

et al. 2024

J Cancer Res Clin Oncol

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Purpose Metabolic reprogramming is currently considered a hallmark of tumor and immune development. It is obviously of interest to identify metabolic enzymes that are associated with clinical prognosis in head and neck squamous cell carcinomas (HNSCC). Methods Candidate genes were screened to construct folate metabolism scores by Cox regression analysis. Functional enrichment between high- and low-folate metabolism groups was explored by GO, KEGG, GSVA, and ssGSEA. EPIC, MCPcounter, and xCell were utilized to explore immune cell infiltration between high- and low-folate metabolism groups. Relevant metabolic scores were calculated and visually analyzed by the “IOBR” software package. Results To investigate the mechanism behind metabolic reprogramming of HNSCC, 2886 human genes associated with 86 metabolic pathways were selected. Folate metabolism is significantly enriched in HNSCC, and that the six-gene (MTHFD1L, MTHFD2, SHMT2, ATIC, MTFMT, and MTHFS) folate score accurately predicts and differentiates folate metabolism levels. Reprogramming of folate metabolism affects CD8T cell infiltration and induces immune escape through the MIF signaling pathway. Further research found that SHMT2, an enzyme involved in folate metabolism, inhibits CD8T cell infiltration and induces immune escape by regulating the MIF/CD44 signaling axis, which in turn promotes HNSCC progression. Conclusions Our study identified a novel and robust folate metabolic signature. A folate metabolic signature comprising six genes was effective in assessing the prognosis and reflecting the immune status of HNSCC patients. The target molecule of folate metabolic reprogramming, SHMT2, probably plays a very important role in HNSCC development and immune escape.

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“…SHMT2 is significantly upregulated in various cancers, including colorectal cancer, glioma, renal cancer, and bladder cancer [ 14 , 15 , 16 , 17 ]. Clinical studies have also shown that high SHMT2 expression is closely related to tumor invasion and prognosis [ 18 ]. Therefore, SHMT2 is expected to be an important target for tumor metabolic reprogramming, and further exploration of its role in tumors is needed.…”

Section: Introductionmentioning

confidence: 99%

SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1α/VEGF/STAT3 Signaling

Wang

et al. 2023

IJMS

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The metabolic enzymes involved in one-carbon metabolism are closely associated with tumor progression and could be potential targets for cancer therapy. Recent studies showed that serine hydroxymethyltransferase 2 (SHMT2), a crucial enzyme in the one-carbon metabolic pathway, plays a key role in tumor proliferation and development. However, the precise role and function of SHMT2 in gastric cancer (GC) remain poorly understood. In this study, we presented evidence that SHMT2 was necessary for hypoxia-inducible factor-1α (HIF1α) stability and contributed to GC cells’ hypoxic adaptation. The analysis of datasets retrieved from The Cancer Genome Atlas and the experimentation with human cell lines revealed a marked increase in SHMT2 expression in GC. The SHMT2 knockdown in MGC803, SGC7901, and HGC27 cell lines inhibited cell proliferation, colony formation, invasion, and migration. Notably, SHMT2 depletion disrupted redox homeostasis and caused glycolytic function loss in GC cells under hypoxic circumstances. Mechanistically, we discovered SHMT2 modulated HIF1α stability, which acted as a master regulator of hypoxia-inducible genes under hypoxic conditions. This, in turn, regulated the downstream VEGF and STAT3 pathways. The in vivo xenograft experiments showed that SHMT2 knockdown markedly reduced GC growth. Our results elucidate the novel function of SHMT2 in stabilizing HIF1α under hypoxic conditions, thus providing a potential therapeutic strategy for GC treatment.

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SHMT2 Induces Stemness and Progression of Head and Neck Cancer

Cited by 8 publications

References 45 publications

A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer

A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer

Construction and validation of a folate metabolism-related gene signature for predicting prognosis in HNSCC

SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1α/VEGF/STAT3 Signaling

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