Mitochondrial calcium uniporter activates TFEB-driven autophagy to promote migration of breast cancer cells

Document Type : Original Article


1 Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, CN 510630, China

2 Department of Breast, Jiangmen Central Hospital, Jiangmen, CN 529030, China

3 Departments of General Surgery and Thyroid Surgery, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, CN 510180, China


Objective(s): Tumor metastasis is the leading cause of death in breast cancer (BC) patients and is a complicated process. Mitochondrial calcium uniporter (MCU), a selective channel responsible for mitochondrial Ca2+ uptake, has been reported to be associated with tumorigenesis and metastasis. The molecular mechanisms of MCU contributing to the migration of BC cells are partially understood. This study investigated the role of MCU in BC cell metastasis and explored the underlying mechanism of MCU-mediated autophagy in BC cell migration.
Materials and Methods: The Kaplan-Meier plotter database was used to analyze the prognostic value of MCU mRNA expression. Western blotting was used to examine the expression level of MCU in 4 paired BC and adjacent normal tissues. The cellular migration capability of BC was measured by transwell migration assay and wound healing assay. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the expression levels of autophagy-related markers. The effects of MCU activation or inhibition on TFEB nuclear translocation in BC cells were detected by laser scanning confocal microscopy.
Results: Expression of MCU was found to be negatively correlated with BC patient prognosis in the Kaplan-Meier plotter database. Compared with the adjacent normal tissues, MCU was markedly up-regulated in the BC tissues. MCU overexpression promoted cellular migration, activated autophagy, and increased TFEB nuclear translocation in BC cells, whereas its knockdown produced the opposite effects.
Conclusion: MCU activates TFEB-driven autophagy to promote BC cell metastasis and provides a potential novel therapeutic target for BC clinical intervention.


Main Subjects

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