title: ZNF32 inhibits autophagy through the mTOR pathway and protects MCF-7 cells from stimulus-induced cell death.
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.
authors: Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Yanyan
authors: Y
authors: Li
authors: Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Le
authors: L
authors: Zhang
authors: Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Kai
authors: K
authors: Li
authors: Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Jun
authors: J
authors: Li
authors: Department of clinical medicine, School of Medicine/Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin, China.
authors: Rong
authors: R
authors: Xiang
authors: Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Jie
authors: J
authors: Zhang
authors: Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors: Hongjiang
authors: H
authors: Li
authors: Biorepository, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Yan
authors: Y
authors: Xu
authors: Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Yuyan
authors: Y
authors: Wei
authors: Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Junping
authors: J
authors: Gao
authors: Division of Experimental Oncology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Ping
authors: P
authors: Lin
authors: Division of Cancer Biotherapy, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Yuquan
authors: Y
authors: Wei
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003958:Diamide / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D010588:Phagosomes / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D051741:Kruppel-Like Transcription Factors; C111477:ZNF32 protein, human; D003958:Diamide; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases