Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/8027
Title: Pluripotent stem cell protein Sox2 confers sensitivity to LSD1 inhibition in cancer cells
Authors: Zhang, X
Lu, F
Wang, J
Yin, F
Xu, Z
Qi, D
Wu, X
Cao, Y
Liang, W
Liu, Y
Sun, H
Ye, T 
Zhang, H
Issue Date: 2013
Publisher: Cell Press
Source: Cell reports, 2013, v. 5, no. 2, p. 445-457 How to cite?
Journal: Cell Reports 
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
URI: http://hdl.handle.net/10397/8027
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2013.09.018
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