Abstract
The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor α (ERRα) induces LSD1 to demethylate the Lys 9 of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRα protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRα from ubiquitination, resulting in overexpression of the latter protein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue) may be a key event to increase ERRα protein, independently of its corresponding mRNA.
Highlights
Lysine Specific Demethylase 1 (LSD1 aka KDM1A) is an enzyme that removes mono- or dimethyl groups from Lys 4 or Lys 9 of histone H3 (H3K4, H3K9, respectively), leading to transcriptional repression or activation, respectively [1,2]
The expression of Estrogen-Related Receptor α (ERRα) was not significantly altered in cancer samples suggesting that the elevation of ERRα protein in tumors does not involved an increase in the corresponding mRNA expression
We had shown that the LSD1 histone demethylase physically interacts with ERRα [34]
Summary
Lysine Specific Demethylase 1 (LSD1 aka KDM1A) is an enzyme that removes mono- or dimethyl groups from Lys 4 or Lys 9 of histone H3 (H3K4, H3K9, respectively), leading to transcriptional repression or activation, respectively [1,2]. The choice between these two types of activities is apparently dictated by the transcriptional (co)-factors with which LSD1 interacts. LSD1 is strongly expressed in various types of cancers, including from the prostate and the breast [11,12,13,14], suggesting an active role in promoting traits of cancer progression. A number of reports have indicated that LSD1 regulates various oncogenic processes, such as enhanced cell motility or metabolic reprograming (reviewed in [15])
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