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Published on: October 28, 2019
ZNF32 inhibits autophagy through the mTOR pathway and protects MCF-7 cells from stimulus-induced cell death
Yanyan Li1, Le Zhang1, Kai Li1
1Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
ZNF32 is a recently identified zinc finger protein and its functions remain largely unknown. Autophagy has been shown to affect cell proliferation and survival. Here, we innovatively show the effect of ZNF32 on cell autophagy and autophagy-associated cell death in breast carcinoma cells and also elucidate its underlying mechanisms. We examined the autophagic activity and LC3 II expression in human carcinoma cell lines with increased or decreased ZNF32 expression. Pharmacological inhibition (rapamycin) or activation (EGF) assays were used to investigate the function of the AKT/mTOR pathway during this process. H2O2- and diamide-induced MCF-7 cell death models were used to elucidate the role of ZNF32-associated autophagy in breast carcinoma cell death. Our results show that increasing ZNF32 expression in MCF-7 cells inhibits autophagy initiation by activating the AKT/mTOR pathway, and further reduced autophagy-associated cell death and maintained MCF-7 cell survival. Conversely, impairing ZNF32 expression by transfecting ZNF32 siRNA strongly promoted autophagy, further augmenting autophagy-associated cell death. Furthermore, correlations between ZNF32 and autophagy were observed in both MCF-7 xenograft tumors and in breast cancer patients. In conclusion, ZNF32 acts as an effective autophagy inhibitor to protect breast cancer cells from excessive stimulus-autophagy-induced cell death.
Insights
Zinc finger protein 32 (ZNF32) inhibits autophagy and autophagy-associated cell death in breast cancer cells by activating the AKT/mTOR pathway, promoting cell survival. Lower ZNF32 levels increase autophagy and cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Autophagy plays a critical role in cell proliferation and survival.
- The function of the recently identified zinc finger protein ZNF32 is largely unknown.
- Understanding ZNF32's role in autophagy is crucial for breast cancer research.
Purpose of the Study:
- To investigate the effect of ZNF32 on autophagy and autophagy-associated cell death in breast carcinoma cells.
- To elucidate the underlying mechanisms of ZNF32's action on autophagy.
- To explore the correlation between ZNF32, autophagy, and breast cancer in vivo and in patients.
Main Methods:
- Examined autophagic activity and LC3 II expression in human carcinoma cell lines with altered ZNF32 expression.
- Utilized pharmacological assays (rapamycin, EGF) to study the AKT/mTOR pathway.
- Employed H2O2- and diamide-induced MCF-7 cell death models to assess ZNF32's role in cell death.
Main Results:
- Increased ZNF32 expression inhibited autophagy initiation via AKT/mTOR pathway activation, reducing autophagy-associated cell death and enhancing MCF-7 cell survival.
- Decreased ZNF32 expression (using siRNA) promoted autophagy and augmented autophagy-associated cell death.
- Correlations between ZNF32 and autophagy were observed in xenograft tumors and human breast cancer patients.
Conclusions:
- ZNF32 functions as an autophagy inhibitor in breast cancer.
- ZNF32 protects breast cancer cells from excessive stimulus-autophagy-induced cell death.
- ZNF32 represents a potential therapeutic target for modulating autophagy in breast cancer treatment.
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