RGD Reference Report - H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. - Rat Genome Database

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H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM.

Authors: Chen, MW  Hua, KT  Kao, HJ  Chi, CC  Wei, LH  Johansson, G  Shiah, SG  Chen, PS  Jeng, YM  Cheng, TY  Lai, TC  Chang, JS  Jan, YH  Chien, MH  Yang, CJ  Huang, MS  Hsiao, M  Kuo, ML 
Citation: Chen MW, etal., Cancer Res. 2010 Oct 15;70(20):7830-40. doi: 10.1158/0008-5472.CAN-10-0833. Epub 2010 Oct 12.
RGD ID: 9589170
Pubmed: PMID:20940408   (View Abstract at PubMed)
DOI: DOI:10.1158/0008-5472.CAN-10-0833   (Journal Full-text)

G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Emerging evidence suggests that G9a is required to maintain the malignant phenotype, but the role of G9a function in mediating tumor metastasis has not been explored. Here, we show that G9a is expressed in aggressive lung cancer cells, and its elevated expression correlates with poor prognosis. RNAi-mediated knockdown of G9a in highly invasive lung cancer cells inhibited cell migration and invasion in vitro and metastasis in vivo. Conversely, ectopic G9a expression in weakly invasive lung cancer cells increased motility and metastasis. Mechanistic investigations suggested that repression of the cell adhesion molecule Ep-CAM mediated the effects of G9a. First, RNAi-mediated knockdown of Ep-CAM partially relieved metastasis suppression imposed by G9a suppression. Second, an inverse correlation between G9a and Ep-CAM expression existed in primary lung cancer. Third, Ep-CAM repression was associated with promoter methylation and an enrichment for dimethylated histone H3K9. G9a knockdown reduced the levels of H3K9 dimethylation and decreased the recruitment of the transcriptional cofactors HP1, DNMT1, and HDAC1 to the Ep-CAM promoter. Our findings establish a functional contribution of G9a overexpression with concomitant dysregulation of epigenetic pathways in lung cancer progression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung adenocarcinoma disease_progressionIEP 9589170 RGD 
lung adenocarcinoma disease_progressionISOEHMT2 (Homo sapiens)9589170; 9589170 RGD 
Neoplasm Metastasis  IMP 9589170associated with lung neoplasmsRGD 
Neoplasm Metastasis  ISOEHMT2 (Homo sapiens)9589170; 9589170associated with lung neoplasmsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ehmt2  (euchromatic histone lysine methyltransferase 2)

Genes (Mus musculus)
Ehmt2  (euchromatic histone lysine N-methyltransferase 2)

Genes (Homo sapiens)
EHMT2  (euchromatic histone lysine methyltransferase 2)


Additional Information