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TrkB Promotes Breast Cancer Metastasis via Suppression of Runx3 and Keap1 Expression
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  • Journal title : Molecules and Cells
  • Volume 39, Issue 3,  2016, pp.258-265
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2310
 Title & Authors
TrkB Promotes Breast Cancer Metastasis via Suppression of Runx3 and Keap1 Expression
Kim, Min Soo; Lee, Won Sung; Jin, Wook;
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 Abstract
In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.
 Keywords
breast cancer;keap1;metastasis;runx3;TrkB;
 Language
English
 Cited by
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Therapeutic Potentials of BDNF/TrkB in Breast Cancer; Current Status and Perspectives, Journal of Cellular Biochemistry, 2017, 118, 9, 2502  crossref(new windwow)
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Identification and Characterization of MCM3 as a Kelch-like ECH-associated Protein 1 (KEAP1) Substrate, Journal of Biological Chemistry, 2016, 291, 45, 23719  crossref(new windwow)
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