The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer

被引:120
作者
Bishop, Jennifer L. [1 ]
Thaper, Daksh [1 ]
Zoubeidi, Amina [1 ]
机构
[1] Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, 2660 Oak St, Vancouver, BC V6H 3Z6, Canada
关键词
STAT3; androgen receptor; prostate cancer; castrate resistance; CSC; metastasis; ENDOTHELIAL GROWTH-FACTOR; SMALL-MOLECULE INHIBITOR; TRANSCRIPTION; 3; STAT3; NF-KAPPA-B; IL-6-INDUCED NEUROENDOCRINE DIFFERENTIATION; ANTI-INTERLEUKIN-6; MONOCLONAL-ANTIBODY; REGULATES ANDROGEN RECEPTOR; SELECTIVE JAK2 INHIBITOR; TUMOR-INITIATING CELLS; HUMAN MULTIPLE-MYELOMA;
D O I
10.3390/cancers6020829
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The signal transducer and activator of transcription (STAT)3 governs essential functions of epithelial and hematopoietic cells that are often dysregulated in cancer. While the role for STAT3 in promoting the progression of many solid and hematopoietic malignancies is well established, this review will focus on the importance of STAT3 in prostate cancer progression to the incurable metastatic castration-resistant prostate cancer (mCRPC). Indeed, STAT3 integrates different signaling pathways involved in the reactivation of androgen receptor pathway, stem like cells and the epithelial to mesenchymal transition that drive progression to mCRPC. As equally important, STAT3 regulates interactions between tumor cells and the microenvironment as well as immune cell activation. This makes it a major factor in facilitating prostate cancer escape from detection of the immune response, promoting an immunosuppressive environment that allows growth and metastasis. Based on the multifaceted nature of STAT3 signaling in the progression to mCRPC, the promise of STAT3 as a therapeutic target to prevent prostate cancer progression and the variety of STAT3 inhibitors used in cancer therapies is discussed.
引用
收藏
页码:829 / 859
页数:31
相关论文
共 221 条
[51]   Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma [J].
Han, Yajun ;
Amin, Hesham A. ;
Franko, Bevin ;
Frantz, Christine ;
Shi, Xinzhe ;
Lai, Raymond .
BLOOD, 2006, 108 (08) :2796-2803
[52]   The hallmarks of cancer [J].
Hanahan, D ;
Weinberg, RA .
CELL, 2000, 100 (01) :57-70
[53]   Hallmarks of Cancer: The Next Generation [J].
Hanahan, Douglas ;
Weinberg, Robert A. .
CELL, 2011, 144 (05) :646-674
[54]   Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia [J].
Hart, S. ;
Goh, K. C. ;
Novotny-Diermayr, V. ;
Tan, Y. C. ;
Madan, B. ;
Amalini, C. ;
Ong, L. C. ;
Kheng, B. ;
Cheong, A. ;
Zhou, J. ;
Chng, W. J. ;
Wood, J. M. .
BLOOD CANCER JOURNAL, 2011, 1 :e44-e44
[55]  
Heath EI, 2010, AM J TRANSL RES, V2, P402
[56]   The JAK2 Inhibitor AZD1480 Potently Blocks Stat3 Signaling and Oncogenesis in Solid Tumors [J].
Hedvat, Michael ;
Huszar, Dennis ;
Herrmann, Andreas ;
Gozgit, Joseph M. ;
Schroeder, Anne ;
Sheehy, Adam ;
Buettner, Ralf ;
Proia, David ;
Kowolik, Claudia M. ;
Xin, Hong ;
Armstrong, Brian ;
Bebernitz, Geraldine ;
Weng, Shaobu ;
Wang, Lin ;
Ye, Minwei ;
McEachern, Kristen ;
Chen, Huawei ;
Morosini, Deborah ;
Bell, Kirsten ;
Alimzhanov, Marat ;
Ioannidis, Stephanos ;
McCoon, Patricia ;
Cao, Zhu A. ;
Yu, Hua ;
Jove, Richard ;
Zinda, Michael .
CANCER CELL, 2009, 16 (06) :487-497
[57]   Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway [J].
Heinrich, PC ;
Behrmann, I ;
Müller-Newen, G ;
Schaper, F ;
Graeve, L .
BIOCHEMICAL JOURNAL, 1998, 334 :297-314
[58]   Galiellalactone is a novel therapeutic candidate against hormone-refractory prostate cancer expressing activated Stat3 [J].
Hellsten, Rebecka ;
Johansson, Martin ;
Dahlman, Anna ;
Dizeyi, Nishtman ;
Sterner, Olov ;
Bjartell, Anders .
PROSTATE, 2008, 68 (03) :269-280
[59]  
Hobisch A, 2001, CLIN CANCER RES, V7, P2941
[60]   Leukemia cell-targeted STAT3 silencing and TLR9 triggering generate systemic antitumor immunity [J].
Hossain, Dewan Md Sakib ;
Dos Santos, Cedric ;
Zhang, Qifang ;
Kozlowska, Anna ;
Liu, Hongjun ;
Gao, Chan ;
Moreira, Dayson ;
Swiderski, Piotr ;
Jozwiak, Agnieszka ;
Kline, Justin ;
Forman, Stephen ;
Bhatia, Ravi ;
Kuo, Ya-Huei ;
Kortylewski, Marcin .
BLOOD, 2014, 123 (01) :15-25