2. Academic Validation
  3. Rab8A promotes breast cancer progression by increasing surface expression of Tropomyosin-related kinase B

Rab8A promotes breast cancer progression by increasing surface expression of Tropomyosin-related kinase B

  • Cancer Lett. 2022 Jun 1;535:215629. doi: 10.1016/j.canlet.2022.215629.
Yansong Liu 1,  Zhonghua Zhang 2,  Xuefeng Gao 3,  Qinghua Ma 1,  Zhiyong Yu 4,  Shuhong Huang 5
Affiliations

Affiliations

  • 1 Department 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.
  • 2 Department of Breast Disease, Dongping County Hospital, Taian, Shandong, China.
  • 3 Department of Breast and Thyroid Surgery, Yinan People's Hospital, Linyi, Shandong, China.
  • 4 Department 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. Electronic address: [email protected].
  • 5 Institute of Basic Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. Electronic address: [email protected].
PMID: 35278612 DOI: 10.1016/j.canlet.2022.215629
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.

Keywords

Brain-derived neurotrophic factor; Protein degradation; Rab8A; Surface expression; TrkB.

Figures
Products
Inhibitors & Agonists
Other Products