Lysine-specific demethylase 1 mediates epidermal growth factor signaling to promote cell migration in ovarian cancer cells.
Epigenetic abnormalities play a vital role in the progression of ovarian cancer. Lysine-specific demethylase 1 (LSD1/KDM1A) acts as an epigenetic regulator and is overexpressed in ovarian tumors. However, the upstream regulator of LSD1 expression in this cancer remains elusive. Here, we show that epidermal growth factor (EGF) signaling upregulates LSD1 protein levels in SKOV3 and HO8910 ovarian cancer cells overexpressing both LSD1 and the EGF receptor. This effect is correlated with a decrease in the dimethylation of H3K4, a major substrate of LSD1, in an LSD1-dependent manner. We also show that inhibition of PI3K/AKT, but not MEK, abolishes the EGF-induced upregulation of LSD1 and cell migration, indicating that the PI3K/PDK1/AKT pathway mediates the EGF-induced expression of LSD1 and cell migration. Significantly, LSD1 knockdown or inhibition of LSD1 activity impairs both intrinsic and EGF-induced cell migration in SKOV3 and HO8910 cells. These results highlight a novel mechanism regulating LSD1 expression and identify LSD1 as a promising therapeutic target for treating metastatic ovarian cancer driven by EGF signaling.
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Genbao
G
Shao
Department of Oncology, the Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, Jiangsu, P. R. China.|Gaochun People's Hospital, Nanjing 211300, Jiangsu, P. R. China.
Jie
J
Wang
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Yuanxia
Y
Li
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Xiuwen
X
Liu
Department of Radiology, the Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu, P. R. China.
Xiaodong
X
Xie
Department of Oncology, the Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, Jiangsu, P. R. China.
Xiaolei
X
Wan
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Meina
M
Yan
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Jie
J
Jin
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Qiong
Q
Lin
Department of Radiology, the Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu, P. R. China.
Haitao
H
Zhu
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Liuping
L
Zhang
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Aihua
A
Gong
School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.|Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China.
Qixiang
Q
Shao
Department of Oncology, the Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, Jiangsu, P. R. China.
Chaoyang
C
Wu
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
D056466:Histone Demethylases; C495195:KDM1A protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors