The role of CREB3L4 in the proliferation of prostate cancer cells

被引:26
作者
Kim, Tae-Hyun [1 ]
Park, Joo-Man [1 ]
Kim, Mi-Young [1 ]
Ahn, Yong-Ho [1 ,2 ]
机构
[1] Yonsei Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 120752, South Korea
[2] Yonsei Univ, Coll Med, Brain Korea PLUS Project Med Sci 21, Seoul 120752, South Korea
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
基金
新加坡国家研究基金会;
关键词
TRANSCRIPTION FACTOR; ANDROGEN RECEPTORS; STRESS; IDENTIFICATION; LIPOGENESIS; EXPRESSION; BINDING; TISP40; AIBZIP; GENES;
D O I
10.1038/srep45300
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The incidence of prostate cancer (PC) is growing rapidly throughout the world, in probable association with the adoption of western style diets. Thus, understanding the molecular pathways triggering the development of PC is crucial for both its prevention and treatment. Here, we investigated the role of the metabolism-associated protein, CREB3L4, in the proliferation of PC cells. CREB3L4 was upregulated by the synthetic androgen, R1881, in LNCaP PC cells (an androgen-dependent cell line). Knockdown of CREB3L4 resulted in decreased androgen-dependent PC cell growth. LNCaP cells transfected with siCREB3L4 underwent G2/M arrest, with upregulation of the proteins cyclin B1, phospho-CDK1, p21Waf1/Cip1, and INCA1, and downregulation of cyclin D1. Moreover, depletion of CREB3L4 resulted in significantly decreased expression of a subset of androgen-receptor (AR) target genes, including PSA, FKBP5, HPGD, KLK2, and KLK4. We also demonstrated that CREB3L4 directly interacts with the AR, and increases the binding of AR to androgen response elements (AREs). We also identified a role for the unfolded protein response (and its surrogate, IRE1 alpha), in activating CREB3L4. Cumulatively, we postulate that CREB3L4 expression is mediated by an AR-IRE1 alpha axis, but is also directly regulated by AR-to-ARE binding. Thus, our study demonstrates that CREB3L4 plays a key role in PC cell proliferation, which is promoted by both AR and IRE1 alpha.
引用
收藏
页数:11
相关论文
共 32 条
[1]   The signalling from endoplasmic reticulum-resident bZIP transcription factors involved in diverse cellular physiology [J].
Asada, Rie ;
Kanemoto, Soshi ;
Kondo, Shinichi ;
Saito, Atsushi ;
Imaizumi, Kazunori .
JOURNAL OF BIOCHEMISTRY, 2011, 149 (05) :507-518
[2]   Inhibitor of Cyclin-dependent Kinase (CDK) Interacting with Cyclin A1 (INCA1) Regulates Proliferation and Is Repressed by Oncogenic Signaling [J].
Baeumer, Nicole ;
Tickenbrock, Lara ;
Tschanter, Petra ;
Lohmeyer, Lisa ;
Diederichs, Sven ;
Baeumer, Sebastian ;
Skryabin, Boris V. ;
Zhang, Feng ;
Agrawal-Singh, Shuchi ;
Koehler, Gabriele ;
Berdel, Wolfgang E. ;
Serve, Hubert ;
Koschmieder, Steffen ;
Mueller-Tidow, Carsten .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (32) :28210-28222
[3]   Transcriptional profiling of genes that are regulated by the endoplasmic reticulum-bound transcription factor AIbZIP/CREB3L4 in prostate cells [J].
Ben Aicha, Sonia ;
Lessard, Julie ;
Pelletier, Melissa ;
Fournier, Andrea ;
Calvo, Ezequiel ;
Labrie, Claude .
PHYSIOLOGICAL GENOMICS, 2007, 31 (02) :295-305
[4]   Tissue-specificity of prostate specific antigens: Comparative analysis of transcript levels in prostate and non-prostatic tissues [J].
Cunha, Ana C. ;
Weigle, Bernd ;
Kiessling, Andrea ;
Bachmann, Michael ;
Rieber, E. Peter .
CANCER LETTERS, 2006, 236 (02) :229-238
[5]   The mutational landscape of lethal castration-resistant prostate cancer [J].
Grasso, Catherine S. ;
Wu, Yi-Mi ;
Robinson, Dan R. ;
Cao, Xuhong ;
Dhanasekaran, Saravana M. ;
Khan, Amjad P. ;
Quist, Michael J. ;
Jing, Xiaojun ;
Lonigro, Robert J. ;
Brenner, J. Chad ;
Asangani, Irfan A. ;
Ateeq, Bushra ;
Chun, Sang Y. ;
Siddiqui, Javed ;
Sam, Lee ;
Anstett, Matt ;
Mehra, Rohit ;
Prensner, John R. ;
Palanisamy, Nallasivam ;
Ryslik, Gregory A. ;
Vandin, Fabio ;
Raphael, Benjamin J. ;
Kunju, Lakshmi P. ;
Rhodes, Daniel R. ;
Pienta, Kenneth J. ;
Chinnaiyan, Arul M. ;
Tomlins, Scott A. .
NATURE, 2012, 487 (7406) :239-243
[6]   The unfolded protein response: controlling cell fate decisions under ER stress and beyond [J].
Hetz, Claudio .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2012, 13 (02) :89-102
[7]   Identification and functional analysis of consensus androgen response elements in human prostate cancer cells [J].
Horie-Inoue, K ;
Bono, H ;
Okazaki, Y ;
Inoue, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 325 (04) :1312-1317
[8]   Identification of Creb3l4 as an essential negative regulator of adipogenesis [J].
Kim, T-H ;
Jo, S-H ;
Choi, H. ;
Park, J-M ;
Kim, M-Y ;
Nojima, H. ;
Kim, J-W ;
Ahn, Y-H .
CELL DEATH & DISEASE, 2014, 5 :e1527-e1527
[9]   Androgen-regulated transcription factor AIbZIP in prostate cancer [J].
Labrie, Claude ;
Lessard, Julie ;
Ben Aicha, Sonia ;
Savard, Marie-Paule ;
Pelletier, Melissa ;
Fournier, Andrea ;
Lavergne, Eliane ;
Calvo, Ezequiel .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2008, 108 (3-5) :237-244
[10]   KLF5 enhances SREBP-1 action in androgen-dependent induction of fatty acid synthase in prostate cancer cells [J].
Lee, Min-Young ;
Moon, Jong-Seok ;
Park, Sahng Wook ;
Koh, Yoo-Kyung ;
Ahn, Yong-Ho ;
Kim, Kyung-Sup .
BIOCHEMICAL JOURNAL, 2009, 417 :313-322