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Rab8A promotes breast cancer progression by increasing surface expression of Tropomyosin-related kinase B
Yansong Liu1, Zhonghua Zhang2, Xuefeng Gao3
1Department of Breast Disease, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Abstract:
Ras-related protein in brain (Rab) proteins are dysregulated in cancer cells and affect the proliferation and metastasis of cancer cells, thereby reducing the survival rate of cancer patients. Brain-derived neurotrophic factor (BDNF) and its receptor Tropomyosin-related kinase B (TrkB) play an important role in the occurrence and development of tumors. In this research, we investigate the interaction of Rab8A and TrkB in regulating the progression of breast cancer. Rab8A is upregulated in breast cancer tissues. The knockdown of Rab8A inhibits the proliferation, migration, and invasion of breast cancer cells through inhibiting TrkB. Moreover, the phosphorylation of AKT and ERK1/2 is suppressed by Rab8A knockdown. Rab8A interacts with TrkB, as revealed by co-immunoprecipitation assay to promote the surface expression of TrkB. However, Rab8A induced no significant changes in TrkB internalization. Functionally, BDNF promotes the expression of Rab8A through inhibiting Rab8A degradation. The TrkB inhibitor K252a blocks cell proliferation, migration and invasion as well as the activation of the AKT and ERK1/2 signaling pathway, which is induced by Rab8A in breast cancer cells. Our results reveal that Rab8A is upregulated by BDNF, and that Rab8A increases the surface expression of TrkB to promote the growth of breast cancer through the activation of the AKT and ERK1/2 signaling pathway. These results suggest that inhibiting Rab8A level could inhibit the progression of breast cancer.
Insights
Ras-related protein in brain (Rab) 8A promotes breast cancer growth by increasing Tropomyosin-related kinase B (TrkB) surface expression. Inhibiting Rab8A may halt cancer progression and improve patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ras-related protein in brain (Rab) proteins are implicated in cancer progression.
- Brain-derived neurotrophic factor (BDNF) and its receptor Tropomyosin-related kinase B (TrkB) signaling are crucial in tumor development.
Purpose of the Study:
- To investigate the interaction between Rab8A and TrkB in breast cancer progression.
- To elucidate the role of Rab8A in regulating TrkB activity and downstream signaling pathways.
Main Methods:
- Analysis of Rab8A expression in breast cancer tissues.
- Knockdown of Rab8A and assessment of cancer cell proliferation, migration, and invasion.
- Co-immunoprecipitation assays to study Rab8A-TrkB interaction.
- Western blotting to evaluate AKT and ERK1/2 phosphorylation.
- Treatment with TrkB inhibitor K252a.
Main Results:
- Rab8A is upregulated in breast cancer tissues.
- Rab8A knockdown inhibits breast cancer cell proliferation, migration, and invasion by reducing TrkB surface expression and suppressing AKT/ERK1/2 phosphorylation.
- Rab8A interacts with TrkB, promoting its surface expression without affecting internalization.
- BDNF upregulates Rab8A by inhibiting its degradation.
- TrkB inhibition blocks Rab8A-induced cancer cell growth and signaling pathway activation.
Conclusions:
- Rab8A, upregulated by BDNF, promotes breast cancer growth by enhancing TrkB surface expression and activating AKT/ERK1/2 signaling.
- Targeting Rab8A presents a potential therapeutic strategy for inhibiting breast cancer progression.
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