PUBLICATION
H3K9 histone methyltransferase, KMT1E/SETDB1, cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis
- Authors
- Wu, P.C., Lu, J.W., Yang, J.Y., Lin, I.H., Ou, D.L., Lin, Y.H., Chou, K.H., Huang, W.F., Wang, W.P., Huang, Y.L., Hsu, C., Lin, L.I., Lin, Y.M., Shen, C.K., Tzeng, T.Y.
- ID
- ZDB-PUB-150211-30
- Date
- 2014
- Source
- Cancer research 74: 7333-43 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Annexin A2/metabolism
- Cell Line, Tumor
- Epigenesis, Genetic*
- Gene Silencing
- Humans
- Lung Neoplasms/genetics*
- Lung Neoplasms/pathology
- Methylation
- Neoplasm Metastasis/genetics*
- Neoplasm Metastasis/pathology
- Promoter Regions, Genetic
- Protein Methyltransferases/genetics*
- Protein Methyltransferases/metabolism
- Signal Transduction/genetics
- Smad2 Protein/metabolism
- Smad3 Protein/metabolism
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 25477335 Full text @ Cancer Res.
Citation
Wu, P.C., Lu, J.W., Yang, J.Y., Lin, I.H., Ou, D.L., Lin, Y.H., Chou, K.H., Huang, W.F., Wang, W.P., Huang, Y.L., Hsu, C., Lin, L.I., Lin, Y.M., Shen, C.K., Tzeng, T.Y. (2014) H3K9 histone methyltransferase, KMT1E/SETDB1, cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis. Cancer research. 74:7333-43.
Abstract
Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFβ-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFβ-mediated lung cancer metastasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping