26. Wissmann M, Yin N, Müller JM, Greschik H, Fodor BD, Jenuwein T, Vogler C, Schneider R,
Günther T, Buettner R, Metzger E, Schüle R (2007) Cooperative demethylation by JMJD2C
and LSD1 promotes androgen receptor-dependent gene expression. Nat Cell Biol 9:347–353
27. Scoumanne A, Chen X (2007) The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners. J Biol Chem 282:15471–15475
28. Lim S, Janzer A, Becker A, Zimmer A, Schüle R, Buettner R, Kirfel J (2010) Lysine-specific
demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker
predicting aggressive biology. Carcinogenesis 31:512–520
29. Wang Y, Zhang H, Chen Y, Sun Y, Yang F, Yu W, Liang J, Sun L, Yang X, Shi L, Li R, Li Y,
Zhang Y, Li Q, Yi X, Shang Y (2009) LSD1 is a subunit of the NuRD complex and targets the
metastasis programs in breast cancer. Cell 138:660–672
30. Hayami S, Kelly JD, Cho H, Yoshimatsu M, Unoki M, Tsunoda T, Field HI, Neal DE,
Yamaue H, Ponder BAJ, Nakamura Y, Hamamoto R (2011) Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer
128:574–586
31. Huang Y, Stewart TM, Wu Y, Baylin SB, Marton LJ, Perkins B, Jones RJ, Woster PM, Casero
RA Jr (2009) Novel oligoamine analogues inhibit lysine-specific demethylase 1 and induce
reexpression of epigenetically silenced genes. Clin Cancer Res 15:7217–7228
32. Cai C, He HH, Chen S, Coleman I, Wang H, Fang Z, Chen S, Nelson PS, Liu XS, Brown M,
Balk SP (2011) Androgen receptor gene expression in prostate cancer is directly suppressed by
the androgen receptor through recruitment of lysine-specific demethylase 1. Cancer Cell
20:457–471
33. Pollock JA, Larrea MD, Jasper JS, McDonnell DP, McCafferty DG (2012) Lysine-specific
histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and
-independent manners. ACS Chem Biol 7:1221–1231
34. Park UH, Kang MR, Kim EJ, Kwon YS, Hur W, Yoon SK, Song BJ, Park JH, Hwang JT, Jeong
JC, Um SJ (2016) ASXL2 promotes proliferation of breast cancer cells by linking ERα to
histone methylation. Oncogene 35:3742–3752
35. Lv T, Yuan D, Miao X, Lv Y, Zhan P, Shen X, Song Y (2012) Over-expression of LSD1
promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS One 7:
e35065
36. Fu X, Zhang P, Yu B (2017) Advances toward LSD1 inhibitors for cancer therapy. Future Med
Chem 9:1227–1242
37. Wang J, Lu F, Ren Q, Sun H, Xu Z, Lan R, Liu Y, Ward D, Quan J, Ye T, Zhang H (2011)
Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem
cell properties. Cancer Res 71:7238–7249
38. 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 (2013) Pluripotent stem cell protein Sox2 confers sensitivity to LSD1 inhibition in cancer
cells. Cell Rep 5:445–457
39. Stewart CA, Byers LA (2015) Altering the course of small cell lung cancer: targeting cancer
stem cells via LSD1 inhibition. Cancer Cell 28:4–6
40. Chen L, Vasilatos SN, Qin Y, Katz TA, Cao C, Wu H, Tasdemir N, Levine KM, Oesterreich S,
Davidson NE, Huang Y (2017) Functional characterization of lysine-specific demethylase
2 (LSD2/KDM1B) in breast cancer progression. Oncotarget 8:81737–81753
41. Liang Y, Vogel JL, Narayanan A, Peng H, Kristie TM (2009) Inhibition of the histone
demethylase LSD1 blocks α-herpesvirus lytic replication and reactivation from latency. Nat
Med 15:1312–1317
42. Narayanan A, Ruyechan WT, Kristie TM (2007) The coactivator host cell factor-1 mediates
Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of
infection. Proc Natl Acad Sci U S A 104:10835–10840
43. Sakane N, Kwon HS, Pagans S, Kaehlcke K, Mizusawa Y, Kamada M, Lassen KG, Chan J,
Greene WC, Schnoelzer M, Ott M (2011) Activation of HIV transcription by the viral Tat
protein requires a demethylation step mediated by lysine-specific demethylase 1 (LSD1/
KDM1). PLoS Pathog 7:e1002184
216
T. Suzuki
Günther T, Buettner R, Metzger E, Schüle R (2007) Cooperative demethylation by JMJD2C
and LSD1 promotes androgen receptor-dependent gene expression. Nat Cell Biol 9:347–353
27. Scoumanne A, Chen X (2007) The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners. J Biol Chem 282:15471–15475
28. Lim S, Janzer A, Becker A, Zimmer A, Schüle R, Buettner R, Kirfel J (2010) Lysine-specific
demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker
predicting aggressive biology. Carcinogenesis 31:512–520
29. Wang Y, Zhang H, Chen Y, Sun Y, Yang F, Yu W, Liang J, Sun L, Yang X, Shi L, Li R, Li Y,
Zhang Y, Li Q, Yi X, Shang Y (2009) LSD1 is a subunit of the NuRD complex and targets the
metastasis programs in breast cancer. Cell 138:660–672
30. Hayami S, Kelly JD, Cho H, Yoshimatsu M, Unoki M, Tsunoda T, Field HI, Neal DE,
Yamaue H, Ponder BAJ, Nakamura Y, Hamamoto R (2011) Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer
128:574–586
31. Huang Y, Stewart TM, Wu Y, Baylin SB, Marton LJ, Perkins B, Jones RJ, Woster PM, Casero
RA Jr (2009) Novel oligoamine analogues inhibit lysine-specific demethylase 1 and induce
reexpression of epigenetically silenced genes. Clin Cancer Res 15:7217–7228
32. Cai C, He HH, Chen S, Coleman I, Wang H, Fang Z, Chen S, Nelson PS, Liu XS, Brown M,
Balk SP (2011) Androgen receptor gene expression in prostate cancer is directly suppressed by
the androgen receptor through recruitment of lysine-specific demethylase 1. Cancer Cell
20:457–471
33. Pollock JA, Larrea MD, Jasper JS, McDonnell DP, McCafferty DG (2012) Lysine-specific
histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and
-independent manners. ACS Chem Biol 7:1221–1231
34. Park UH, Kang MR, Kim EJ, Kwon YS, Hur W, Yoon SK, Song BJ, Park JH, Hwang JT, Jeong
JC, Um SJ (2016) ASXL2 promotes proliferation of breast cancer cells by linking ERα to
histone methylation. Oncogene 35:3742–3752
35. Lv T, Yuan D, Miao X, Lv Y, Zhan P, Shen X, Song Y (2012) Over-expression of LSD1
promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS One 7:
e35065
36. Fu X, Zhang P, Yu B (2017) Advances toward LSD1 inhibitors for cancer therapy. Future Med
Chem 9:1227–1242
37. Wang J, Lu F, Ren Q, Sun H, Xu Z, Lan R, Liu Y, Ward D, Quan J, Ye T, Zhang H (2011)
Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem
cell properties. Cancer Res 71:7238–7249
38. 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 (2013) Pluripotent stem cell protein Sox2 confers sensitivity to LSD1 inhibition in cancer
cells. Cell Rep 5:445–457
39. Stewart CA, Byers LA (2015) Altering the course of small cell lung cancer: targeting cancer
stem cells via LSD1 inhibition. Cancer Cell 28:4–6
40. Chen L, Vasilatos SN, Qin Y, Katz TA, Cao C, Wu H, Tasdemir N, Levine KM, Oesterreich S,
Davidson NE, Huang Y (2017) Functional characterization of lysine-specific demethylase
2 (LSD2/KDM1B) in breast cancer progression. Oncotarget 8:81737–81753
41. Liang Y, Vogel JL, Narayanan A, Peng H, Kristie TM (2009) Inhibition of the histone
demethylase LSD1 blocks α-herpesvirus lytic replication and reactivation from latency. Nat
Med 15:1312–1317
42. Narayanan A, Ruyechan WT, Kristie TM (2007) The coactivator host cell factor-1 mediates
Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of
infection. Proc Natl Acad Sci U S A 104:10835–10840
43. Sakane N, Kwon HS, Pagans S, Kaehlcke K, Mizusawa Y, Kamada M, Lassen KG, Chan J,
Greene WC, Schnoelzer M, Ott M (2011) Activation of HIV transcription by the viral Tat
protein requires a demethylation step mediated by lysine-specific demethylase 1 (LSD1/
KDM1). PLoS Pathog 7:e1002184
216
T. Suzuki