BDNF activates TrkB/PLCγ1 signaling pathway to promote proliferation and invasion of ovarian cancer cells through inhibition of apoptosis

被引:2
作者
Xu, Y. [1 ]
Jiang, W-G [2 ]
Wang, H-C [1 ]
Martin, T. [2 ]
Zeng, Y-X [3 ]
Zhang, J. [3 ]
Qi, Y-S [1 ]
机构
[1] Zibo Matern & Child Hlth Hosp, Dept Gynaecol, Zibo, Peoples R China
[2] Cardiff Univ, Sch Med, CCMRC, Henry Wellcome Bldg,Heath Pk, Cardiff, S Glam, Wales
[3] PLA Navy Qingdao Special Serv Recuperat Ctr, Qingdao, Shandong, Peoples R China
关键词
BDNF; TrkB; PLC gamma 1; Ovarian cancer; Proliferation; Invasion; Apoptosis; EXPRESSION; MIGRATION; RECEPTOR; GROWTH; TRKB;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
OBJECTIVE: Abnormal expression and activation of tropomyosin-related kinase receptor B (TrkB) are observed in many pathological conditions, including many types of cancer. We try to explore the relationship between ovarian cancer and Brain-derived neurotrophic factor (BDNF), a ligand of TrkB. MATERIALS AND METHODS: Human ovarian cancer cell line SKOV-3 was used in this study. qPCR, immunohistochemistry, and immunoblot were used to assay BDNF and TrkB expression level. Scratch assay was used to test the cell motility, and transwell assay was used to test the cell migration ability. RESULTS: We found that BDNF promotes the proliferation and invasion of human ovarian cancer SKOV-3 cells depend on the activation of TrkB. To illuminate the downstream pathway of BDNF/TrkB, we silenced AKT1 and PLC gamma 1 by siRNA. The functional assay showed that activated PLC gamma 1 signaling pathway is necessary for the proliferation and invasion of cancer cells other than the AKT pathway. Further study showed that PLC gamma 1 could inhibit the apoptosis of cancer cells. CONCLUSIONS: BDNF triggers TrkB/PLC gamma 1 signaling pathway to promote proliferation and invasion of ovarian cancer cells through inhibition of apoptosis.
引用
收藏
页码:5093 / 5100
页数:8
相关论文
共 16 条
[1]  
[Anonymous], 2018, ANTI-CANCER DRUG, DOI [DOI 10.3322/caac.20115, DOI 10.1097/CAD.0000000000000617]
[2]  
Asgharzadeh S, 2006, JNCI-J NATL CANCER I, V98, P1193, DOI 10.1093/jnci/djj330
[3]   Tyrosine kinase B receptor and BDNF expression in ovarian cancers - Effect on cell migration, angiogenesis and clinical outcome [J].
Au, Christy W. H. ;
Siu, Michelle K. Y. ;
Liao, Xiaoyun ;
Wong, Esther S. Y. ;
Ngan, Hextan Y. S. ;
Tam, Kar Fai ;
Chan, Dominic C. W. ;
Chan, Queeny K. Y. ;
Cheung, Annie N. Y. .
CANCER LETTERS, 2009, 281 (02) :151-161
[4]   Neuroblastoma: Biological insights into a clinical enigma [J].
Brodeur, GM .
NATURE REVIEWS CANCER, 2003, 3 (03) :203-216
[5]   Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project [J].
Gilbert, Lucy ;
Basso, Olga ;
Sampalis, John ;
Karp, Igor ;
Martins, Claudia ;
Feng, Jing ;
Piedimonte, Sabrina ;
Quintal, Louise ;
Ramanakumar, Agnihotram V. ;
Takefman, Janet ;
Grigorie, Maria S. ;
Artho, Giovanni ;
Krishnamurthy, Srinivasan .
LANCET ONCOLOGY, 2012, 13 (03) :285-291
[6]   EXPRESSION AND FUNCTION OF TRK-B AND BDNF IN HUMAN NEUROBLASTOMAS [J].
NAKAGAWARA, A ;
AZAR, CG ;
SCAVARDA, NJ ;
BRODEUR, GM .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (01) :759-767
[7]   Phospholipase signalling networks in cancer [J].
Park, Jong Bae ;
Lee, Chang Sup ;
Jang, Jin-Hyeok ;
Ghim, Jaewang ;
Kim, Youn-Jae ;
You, Sungyoung ;
Hwang, Daehee ;
Suh, Pann-Ghill ;
Ryu, Sung Ho .
NATURE REVIEWS CANCER, 2012, 12 (11) :782-792
[8]   Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer [J].
Patani, Neill ;
Jiang, Wen G. ;
Mokbel, Kefah .
CANCER CELL INTERNATIONAL, 2011, 11
[9]   A neurotrophin axis in myeloma: TrkB and BDNF promote tumor-cell survival [J].
Pearse, RN ;
Swendeman, SL ;
Li, Y ;
Rafii, D ;
Hempstead, BL .
BLOOD, 2005, 105 (11) :4429-4436
[10]   The Trk tyrosine kinase inhibitor K252a regulates growth of lung adenocarcinomas [J].
Perez-Pinera, P. ;
Hernandez, T. ;
Garcia-Suarez, O. ;
de Carlos, F. ;
Germana, A. ;
del Valle, M. ;
Astudillo, A. ;
Vega, J. A. .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2007, 295 (1-2) :19-26