TY - JOUR
T1 - Therapeutic Potentials of BDNF/TrkB in Breast Cancer; Current Status and Perspectives
AU - Tajbakhsh, Amir
AU - Mokhtari-Zaer, Amin
AU - Rezaee, Mehdi
AU - Afzaljavan, Fahimeh
AU - Rivandi, Mehdi
AU - Hassanian, Seyed Mahdi
AU - Ferns, Gordon A.
AU - Pasdar, Alireza
AU - Avan, Amir
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to stimulate breast cancer cell growth and metastasis via tyrosine kinase receptors TrkA, TrkB, and the p75NTR death receptor. The aberrant activation of BDNF/TrkB pathways can modulate several signaling pathways, including Akt/PI3K, Jak/STAT, NF-kB, UPAR/UPA, Wnt/β-catenin, and VEGF pathways as well as the ER receptor. Several microRNAs have been identified that are involved in the modulation of BDNF/TrkB pathways. These include miR-206, miR-204, MiR-200a/c, MiR-210, MiR-134, and MiR-191; and these may be of value as prognostic and predictive biomarkers for detecting patients at high risk of developing breast cancer. It has been also been demonstrated that a high expression of genes involved in the BDNF pathway in breast cancer is associated with poor clinical outcome and reduced survival of patients. Several approaches have been developed for targeting this pathway, for example TKr inhibitors (AZD6918, CEP-701) and RNA interference. The aim of the current review was to provide an overview of the role of BDNF/TrkB pathways in the pathogenesis of breast cancer and its value as a potential therapeutic target. J. Cell. Biochem. 118: 2502–2515, 2017.
AB - Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to stimulate breast cancer cell growth and metastasis via tyrosine kinase receptors TrkA, TrkB, and the p75NTR death receptor. The aberrant activation of BDNF/TrkB pathways can modulate several signaling pathways, including Akt/PI3K, Jak/STAT, NF-kB, UPAR/UPA, Wnt/β-catenin, and VEGF pathways as well as the ER receptor. Several microRNAs have been identified that are involved in the modulation of BDNF/TrkB pathways. These include miR-206, miR-204, MiR-200a/c, MiR-210, MiR-134, and MiR-191; and these may be of value as prognostic and predictive biomarkers for detecting patients at high risk of developing breast cancer. It has been also been demonstrated that a high expression of genes involved in the BDNF pathway in breast cancer is associated with poor clinical outcome and reduced survival of patients. Several approaches have been developed for targeting this pathway, for example TKr inhibitors (AZD6918, CEP-701) and RNA interference. The aim of the current review was to provide an overview of the role of BDNF/TrkB pathways in the pathogenesis of breast cancer and its value as a potential therapeutic target. J. Cell. Biochem. 118: 2502–2515, 2017.
KW - BRAIN-DERIVED NEUROTROPHIC FACTOR
KW - BREAST CANCER
KW - EPIGENETICS
KW - PHARMACOLOGICAL MODULATORS
KW - RISK FACTOR
UR - http://www.scopus.com/inward/record.url?scp=85019571705&partnerID=8YFLogxK
U2 - 10.1002/jcb.25943
DO - 10.1002/jcb.25943
M3 - Article
C2 - 28230291
AN - SCOPUS:85019571705
SN - 0730-2312
VL - 118
SP - 2502
EP - 2515
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 9
ER -