ArticleCancer science2017
Effects of SMYD2-mediated EML4-ALK methylation on the signaling pathway and growth in non-small-cell lung cancer cells.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Lysine methyltransferase SMYD2 enhances androgen receptor signaling to modulate CRPC cell resistance to enzalutamide.Oncogene · 2024Article
- Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.Biomedicines · 2024Review
- Non-small Cell Lung Cancer Epigenomes Exhibit Altered DNA Methylation in Smokers and Never-smokers.Genomics, proteomics & bioinformatics · 2023Article
- Lysine methyltransferase SMYD2 inhibits antiviral innate immunity by promoting IRF3 dephosphorylation.Cell death & disease · 2023Article
- Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis.Experimental & molecular medicine · 2023Article
- Zinc finger myeloid Nervy DEAF-1 type (ZMYND) domain containing proteins exert molecular interactions to implicate in carcinogenesis.Discover oncology · 2022Review
- DNA and histone modifications as potent diagnostic and therapeutic targets to advance non-small cell lung cancer management from the perspective of 3P medicine.The EPMA journal · 2022Review
- SMYD2 facilitates cancer cell malignancy and xenograft tumor development through ERBB2-mediated FUT4 expression in colon cancer.Molecular and cellular biochemistry · 2022Article
- Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer.World journal of gastroenterology · 2022Review
- Baicalein Inhibits the SMYD2/RPS7 Signaling Pathway to Inhibit the Occurrence and Metastasis of Lung Cancer.Journal of oncology · 2022Article
- A Non-Synonymous Point Mutation in a WD-40 Domain Repeat of EML5 Leads to Decreased Bovine Sperm Quality and Fertility.Frontiers in cell and developmental biology · 2022Article
- Novel insights into SMYD2 and SMYD3 inhibitors: from potential anti-tumoural therapy to a variety of new applications.Molecular biology reports · 2021Review
- Inhibition of UBA5 Expression and Induction of Autophagy in Breast Cancer Cells by Usenamine A.Biomolecules · 2021Article
- SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7.Cell death & disease · 2021Article
- The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells.Oncology letters · 2020Article
- Characterizing the Role of SMYD2 in Mammalian Embryogenesis-Future Directions.Veterinary sciences · 2020Article
- Histone methyltransferase SMYD2: ubiquitous regulator of disease.Clinical epigenetics · 2019Review
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A specific subtype of non-small-cell lung cancer (NSCLC) characterized with an EML4-ALK fusion gene, which drives constitutive oncogenic activation of anaplastic lymphoma kinase (ALK), shows a good clinical response to ALK inhibitors. We have reported multiple examples implying the biological significance of methylation on non-histone proteins including oncogenic kinases in human carcinogenesis. Through the process to search substrates for various methyltransferases using an in vitro methyltransferase assay, we found that a lysine methyltransferase, SET and MYND domain-containing 2 (SMYD2), could methylate lysine residues 1451, 1455, and 1610 in ALK protein. Knockdown of SMYD2 as well as treatment with a SMYD2 inhibitor in two NSCLC cell lines with an EML4-ALK gene significantly attenuated the phosphorylation levels of the EML4-ALK protein. Substitutions of each of these three lysine residues to an alanine partially or almost completely diminished in vitro methylation of ALK. In addition, we found that exogenous introduction of EML4-ALK protein with the substitution of lysine 1610 to an alanine in these two cell lines reduced the phosphorylation levels of AKT, one of the downstream oncogenic molecules in the EML4-ALK pathway, and suppressed the growth of the two cell lines. We further showed that the combination of a SMYD2 inhibitor and an ALK inhibitor additively suppressed the growth of these two NSCLC cells, compared with single-agent treatment. Our results shed light on a novel mechanism that modulates the kinase activity of the ALK fused gene product and imply that SMYD2-mediated ALK methylation might be a promising target for development of a novel class of treatment for tumors with the ALK fused gene.
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