Negative regulation of SH2B3 by SMYD5 controls epithelial-mesenchymal transition in lung cancer

The main cause of death in lung cancer patients is metastasis. Thus, efforts to suppress micrometastasis or distant metastasis in lung cancer, identify therapeutic targets and develop related drugs are ongoing. In this study, we identified SET and MYND domain-containing protein 5 (SMYD5) as a novel...

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Published in:Molecules and cells 2024, 47(1), , pp.1-9
Main Authors: Tae, In Hwan, Ryu, Tae Young, Kang, Yunsang, Lee, Jinkwon, Kim, Kwanho, Lee, Jeong Min, Kim, Hee-Won, Ko, Jung Heon, Kim, Dae-Soo, Son, Mi-Young, Cho, Hyun-Soo
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Cell Line, Tumor
Cell Movement
Epithelial-mesenchymal transition
Epithelial-Mesenchymal Transition - genetics
Gene Expression Regulation, Neoplastic
Humans
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Metastasis
Neoplasm Invasiveness
SMYD5
생물학
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Summary:The main cause of death in lung cancer patients is metastasis. Thus, efforts to suppress micrometastasis or distant metastasis in lung cancer, identify therapeutic targets and develop related drugs are ongoing. In this study, we identified SET and MYND domain-containing protein 5 (SMYD5) as a novel metastasis regulator in lung cancer and found that SMYD5 was overexpressed in lung cancer based on both RNA-sequencing analysis results derived from the TCGA portal and immunohistochemical analysis results; knockdown of SMYD5 inhibited cell migration and invasion by changing epithelial-mesenchymal transition markers and MMP9 expression in NCI-H1299 and H1703 cell lines. Additionally, SMYD5 knockdown increased Src homology 2-b3 expression by decreasing the level of H4K20 trimethylation. Furthermore, in an in vitro epithelial-mesenchymal transition system using TGF-β treatment, SMYD5 knockdown resulted in reduced cell migration and invasion in the highly invasive NCI-H1299 and H1703 cell lines. Based on these findings, we propose that SMYD5 could serve as a potential therapeutic target for lung cancer treatment and that cotreatment with an SMYD5 inhibitor and chemotherapy may enhance the therapeutic effect of lung cancer treatment.
ISSN:1016-8478
0219-1032
DOI:10.1016/j.mocell.2024.100067