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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.3
- 수록면
- 258 - 265 (8page)
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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 inhibi-tion of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces pro-liferation. 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.
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참고문헌 (40)
참고문헌 신청
Bardelli, A. / 2003 / Mutational analysis of the tyrosine kinome in colorectal cancers / Science 300:949
Cancer Genome Atlas, N. / 2012 / Comprehensive molecular portraits of human breast tumours / Nature 490:61~70
Chao, M. V. / 2002 / Neurotrophins : to cleave or not to cleave / Neuron 33:9~12
Chen, L. F / 2012 / Tumor suppressor function of RUNX3 in breast cancer / J. Cell Biochem 113:1470~1477
Chi, X. Z. / 2005 / RUNX3suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1)expression in cooperation with transforming growth factor(Bierie and Moses)-activated SMAD / Mol. Cell Biol 25:8097~8107
Cancer Genome Atlas, N. / 2012 / Comprehensive molecular portraits of human breast tumours / Nature 490:61~70
Chao, M. V. / 2002 / Neurotrophins : to cleave or not to cleave / Neuron 33:9~12
Chen, L. F / 2012 / Tumor suppressor function of RUNX3 in breast cancer / J. Cell Biochem 113:1470~1477
Chi, X. Z. / 2005 / RUNX3suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1)expression in cooperation with transforming growth factor(Bierie and Moses)-activated SMAD / Mol. Cell Biol 25:8097~8107
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