Tumor-suppressive functions of protein lysine methyltransferases

Protein lysine methyltransferases (PKMTs) play crucial roles in histone and nonhistone modifications, and their dysregulation has been linked to the development and progression of cancer. While the majority of studies have focused on the oncogenic functions of PKMTs, extensive evidence has indicated that these enzymes also play roles in tumor suppression by regulating the stability of p53 and β-catenin, promoting α-tubulin-mediated genomic stability, and regulating the transcription of oncogenes and tumor suppressors. Despite their contradictory roles in tumorigenesis, many PKMTs have been identified as potential therapeutic targets for cancer treatment. However, PKMT inhibitors may have unintended negative effects depending on the specific cancer type and target enzyme. Therefore, this review aims to comprehensively summarize the tumor-suppressive effects of PKMTs and to provide new insights into the development of anticancer drugs targeting PKMTs. PKMT inhibitors: a double-edged sword in cancer treatment The review summarizes the tumor-suppressive role of protein lysine methyltransferases (PKMTs), a group of enzymes that add a methyl group to the lysine residues of proteins. The authors highlight three PKMTs – SETD2, SETD7, and EZH2 – which have been found to suppress tumor growth in various types of cancer. For instance, SETD2 has been shown to maintain genomic stability and enhance DNA damage repair in clear cell renal cell carcinoma. Similarly, SETD7 has been found to inhibit cell proliferation and migration in gastric cancer. EZH2, on the other hand, has been shown to suppress tumor growth in lung adenocarcinoma and myelodysplastic syndrome. The authors also discuss the potential of PKMT inhibitors as therapeutic agents for cancer treatment. However, they caution that due to the pleiotropic roles of these enzymes in tumorigenesis, careful consideration is needed when using PKMT inhibitors for cancer therapy. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.