Back to Search
Start Over
KDM1A promotes tumor cell invasion by silencing TIMP3 in non-small cell lung cancer cells.
- Source :
-
Oncotarget [Oncotarget] 2016 May 10; Vol. 7 (19), pp. 27959-74. - Publication Year :
- 2016
-
Abstract
- Epigenetic regulation plays an important role in tumor metastasis. KDM1A is a histone demethylase specific for H3K4me2/me1 demethylation, and has been found to be overexpressed in many cancers, including non-small cell lung cancer (NSCLC). However, the role of KDM1A in lung cancer remains unclear. Here, we show that KDM1A promotes cancer metastasis in NSCLC cells by repressing TIMP3 (tissue inhibitor of metalloproteinase 3) expression. Consistently with this, overexpression of TIMP3 inhibited MMP2 expression and JNK phosphorylation, both of which are known to be important for cell invasion and migration. Importantly, knockdown of TIMP3 in KDM1A-deficient cells rescued the metastatic capability of NSCLC cells. These findings were also confirmed by pharmacological inhibition assays. We further demonstrate that KDM1A removes H3K4me2 at the promoter of TIMP3, thus repressing the transcription of TIMP3. Finally, high expression of KDM1A and low expression of TIMP3 significantly correlate with a poor prognosis in NSCLC patients. This study establishes a mechanism by which KDM1A promotes cancer metastasis in NSCLC cells, and we suggest that KDM1A may be a potential therapeutic target for NSCLC treatment.<br />Competing Interests: The authors declare no potential conflicts of interest.
- Subjects :
- Animals
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung mortality
Cell Line, Tumor
Cell Movement genetics
Gene Silencing
Heterografts
Histone Demethylases genetics
Humans
Kaplan-Meier Estimate
Lung Neoplasms genetics
Lung Neoplasms mortality
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness genetics
Tissue Inhibitor of Metalloproteinase-3 genetics
Carcinoma, Non-Small-Cell Lung pathology
Gene Expression Regulation, Neoplastic physiology
Histone Demethylases metabolism
Lung Neoplasms pathology
Tissue Inhibitor of Metalloproteinase-3 biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27058897
- Full Text :
- https://doi.org/10.18632/oncotarget.8563