SHMT2 Induces Stemness and Progression of Head and Neck Cancer.

Various enzymes in the one-carbon metabolic pathway are closely related to the development of tumors, and they can all be potential targets for cancer therapy. Serine hydroxymethyltransferase2 (), a key metabolic enzyme, is very important for the proliferation and growth of cancer cells. However, the function and mechanism of in head and neck cancer (HNC) are not clear. An analysis of The Cancer Genome Atlas (TCGA) data showed that the expression of was higher in tumor tissue than in normal tissue, and its expression was significantly associated with male sex, aggressive histological grade, lymph node metastasis, distant metastasis, advanced TNM stage, and lymphovascular invasion in HNC. knockdown in FADU and SNU1041 cell lines significantly inhibited cell proliferation, colony formation, migration, and invasion. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using TCGA data revealed that was closely related to cancer stem cell regulation and maintenance. Furthermore, we found that silencing inhibited the expression of stemness markers and tumor spheroid formation compared with a control group. On the contrary, stemness markers were significantly increased after overexpression in HEP-2 cells. Interestingly, we found that knocking down reduced the expression of genes related to the Notch and Wnt pathways. Finally, silencing significantly reduced tumor growth and decreased stemness markers in a xenograft model. Taken together, our study suggests that targeting may play an important role in inhibiting HNC progression.