Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Oct 31;5(2):445-57.
doi: 10.1016/j.celrep.2013.09.018. Epub 2013 Oct 17.

Pluripotent Stem Cell Protein Sox2 Confers Sensitivity to LSD1 Inhibition in Cancer Cells

Affiliations
Free article

Pluripotent Stem Cell Protein Sox2 Confers Sensitivity to LSD1 Inhibition in Cancer Cells

Xiaoming Zhang et al. Cell Rep. .
Free article

Abstract

Gene amplification of Sox2 at 3q26.33 is a common event in squamous cell carcinomas (SCCs) of the lung and esophagus, as well as several other cancers. Here, we show that the expression of LSD1/KDM1 histone demethylase is significantly elevated in Sox2-expressing lung SCCs. LSD1-specific inhibitors selectively impair the growth of Sox2-expressing lung SCCs, but not that of Sox2-negative cells. Sox2 expression is associated with sensitivity to LSD1 inhibition in lung, breast, ovarian, and other carcinoma cells. Inactivation of LSD1 reduces Sox2 expression, promotes G1 cell-cycle arrest, and induces genes for differentiation by selectively modulating the methylation states of histone H3 at lysines 4 (H3K4) and 9 (H3K9). Reduction of Sox2 further suppresses Sox2-dependent lineage-survival oncogenic potential, elevates trimethylation of histone H3 at lysine 27 (H3K27) and enhances growth arrest and cellular differentiation. Our studies suggest that LSD1 serves as a selective epigenetic target for therapy in Sox2-expressing cancers.

Similar articles

See all similar articles

Cited by 43 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback