Journal
CELL DEATH & DISEASE
Volume 12, Issue 9, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-021-04140-6
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Funding
- Department of Science and Technology of Liaoning province [2019-MS-363, 2017225028]
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EMP3 acts as a potential tumor suppressor in breast cancer by inhibiting cell cycle progression, DNA repair, and stem-like properties, leading to enhanced sensitivity of breast cancer cells to DNA-damaging agents.
Enhanced DNA damage repair capacity attenuates cell killing of DNA-damaging chemotherapeutic agents. In silico analysis showed that epithelial membrane protein 3 (EMP3) is associated with favorable survival, and negatively regulates cell cycle S-phase. Consistently, loss and gain of function studies demonstrated that EMP3 inhibits breast cancer cell S-phage entry, DNA replication, DNA damage repair, and stem-like properties. Moreover, EMP3 blocks Akt-mTOR signaling activation and induces autophagy. EMP3 negatively modulates BRCA1 and RAD51 expression, indicating EMP3 suppresses homologous recombination repair of DNA double-strand breaks. Accordingly, EMP3 sensitizes breast cancer cells to the DNA-damaging drug Adriamycin. EMP3 downregulates YTHDC1, a RNA-binding protein involved in m6a modification, which at least in part mediates the effects of EMP3 on breast cancer cells. Taken together, these data indicate that EMP3 is a putative tumor suppressor in breast cancer, and EMP3 downregulation may be responsible for breast cancer chemoresistance.
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