LSD1 sustains pancreatic cancer growth via maintaining HIF1α-dependent glycolytic process

被引：75

作者：

Qin, Yi ^{[1
,2
,3
]}

Zhu, Wenwei ^{[1
,3
]}

Xu, Wenyan ^{[1
,3
]}

Zhang, Bo ^{[1
,2
,3
]}

Shi, Si ^{[1
,2
,3
]}

Ji, Shunrong ^{[1
,2
,3
]}

Liu, Jiang ^{[1
,2
,3
]}

Long, Jiang ^{[1
,2
,3
]}

Liu, Chen ^{[1
,2
,3
]}

Liu, Liang ^{[1
,2
,3
]}

Xu, Jin ^{[1
,3
]}

Yu, Xianjun ^{[1
,2
,3
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr, Dept Pancreat & Hepatobiliary Surg, Shanghai 200032, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China

[3] Fudan Univ, Pancreat Canc Inst, Shanghai 200032, Peoples R China

来源：

CANCER LETTERS | 2014年 / 347卷 / 02期

基金：

美国国家科学基金会;

关键词：

LSD1; Pancreatic cancer; Glycolysis; HIF1; alpha; HISTONE DEMETHYLATION; EPIGENETIC BIOMARKERS; DOWN-REGULATION; E-CADHERIN; HYPOXIA; TUMOR; METASTASIS; EXPRESSION; CARCINOMA; CELLS;

D O I：

10.1016/j.canlet.2014.02.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The histone demethylase LSD1 (lysine specific demethylase 1) plays an important role in the epigenetic regulation of gene transcription. Our study investigated the role of LSD1 in pancreatic cancer and demonstrated that LSD1 was significantly up-regulated in pancreatic cancer patient tissue samples, and elevated LSD1 protein levels positively correlated with overall survival of pancreatic cancer patients. Using in vitro and in vivo models, we demonstrated that knock-down of LSD1 repressed proliferation and tumorigenicity of pancreatic cancer cells. Mechanistically, our study demonstrated that LSD1 synergized with HIFI a (hypoxia inducible factor-1 alpha) in maintaining glycolytic process, which fueled pancreatic cancer uncontrolled proliferation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：225 / 232

页数：8

共 37 条

[1] The histone LSD1 demethylase in stemness and cancer transcription programs [J].

Amente, Stefano ;

Lania, Luigi ;

Majello, Barbara .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2013, 1829 (10) :981-986

[2] Hypoxia, DNA repair and genetic instability [J].

Bristow, Robert G. ;

Hill, Richard P. .

NATURE REVIEWS CANCER, 2008, 8 (03) :180-192

[3] HDAC2 promotes cell migration/invasion abilities through HIF-1α stabilization in human oral squamous cell carcinoma [J].

Chang, Cheng-Chi ;

Lin, Been-Ren ;

Chen, Szu-Ta ;

Hsieh, Tsung-Han ;

Li, Yue-Ju ;

Kuo, Mark Y. -P. .

JOURNAL OF ORAL PATHOLOGY & MEDICINE, 2011, 40 (07) :567-575

[4] Profilin1 Sensitizes Pancreatic Cancer Cells to Irradiation by Inducing Apoptosis and Reducing Autophagy [J].

Cheng, H. ;

Li, J. ;

Liu, C. ;

Yao, W. ;

Xu, Y. ;

Frank, T. S. ;

Cai, X. ;

Shi, S. ;

Lu, Y. ;

Qin, Y. ;

Liu, L. ;

Xu, J. ;

Long, J. ;

Ni, Q. -X. ;

Li, M. ;

Yu, X. -J. .

CURRENT MOLECULAR MEDICINE, 2013, 13 (08) :1368-1375

[5] Hypoxia-inducible factor 1 alpha mediates epidermal growth factor-induced down-regulation of E-cadherin expression and cell invasion in human ovarian cancer cells [J].

Cheng, Jung-Chien ;

Klausen, Christian ;

Leung, Peter C. K. .

CANCER LETTERS, 2013, 329 (02) :197-206

[6] LSD1 and the chemistry of histone demethylation [J].

Culhane, Jeffrey C. ;

Cole, Philip A. .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2007, 11 (05) :561-568

[7] Hypoxia, HIF1 and glucose metabolism in the solid tumour [J].

Denko, Nicholas C. .

NATURE REVIEWS CANCER, 2008, 8 (09) :705-713

[8] Road to early detection of pancreatic cancer: Attempts to utilize epigenetic biomarkers [J].

Fukushige, Shinichi ;

Horii, Akira .

CANCER LETTERS, 2014, 342 (02) :231-237

[9] HDAC4 Protein Regulates HIF1α Protein Lysine Acetylation and Cancer Cell Response to Hypoxia [J].

Geng, Hao ;

Harvey, Chris T. ;

Pittsenbarger, Janet ;

Liu, Qiong ;

Beer, Tomasz M. ;

Xue, Changhui ;

Qian, David Z. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (44) :38095-38102

[10]

Gort EH, 2008, CURR MOL MED, V8, P60

← 1 2 3 4 →