Fang-Ming Chen1,2,3,4, Li-Ju Huang5, Fu Ou-Yang1,2, Jung-Yu Kan1,2, Li-Chun Kao1,2, Ming-Feng Hou6,7,8,9. 1. Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC. 2. Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, No. 68, Zhonghua 3rd Rd., Qianjin Dist., Kaohsiung, 801, Taiwan, ROC. 3. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC. 4. Drug Development and Value Creation Research Center, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC. 5. Center of Teaching and Research, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC. 6. Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC. 1028247@kmtth.org.tw. 7. Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, No. 68, Zhonghua 3rd Rd., Qianjin Dist., Kaohsiung, 801, Taiwan, ROC. 1028247@kmtth.org.tw. 8. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC. 1028247@kmtth.org.tw. 9. Drug Development and Value Creation Research Center, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC. 1028247@kmtth.org.tw.
Abstract
PURPOSE: Mitochondrial unfolding protein are abundant in breast cancer cells, but the mechanism by which breast cancer cells resist apoptosis is still not fully elucidated. In this study, we explored the role of mitochondrial unfolded protein response (mtUPR)-related proteins in four types of breast cancer tissues. METHODS: Mitochondrial fractions were taken from four breast cancer tissues (luminal A, luminal B, Her2 -overexpression, and TNBC) and the expression of mitochondrial polyubiquitinated proteins was observed by western blot and ELISA. In addition, the expression of hsp10, hsp60, and clpp in mitochondria was observed by western blot in breast cancer tissues and adjacent tissues, and confirmed by ELISA. The expression levels of hsp10 and hsp60 were correlated with clinicopathological parameters in 114 breast cancer patients. RESULTS: We found an increase in the performance of mitochondrial polyubiquitinated proteins in breast cancer tissues of luminal A, luminal B, Her2-overexpression, and TNBC. The mitochondrial hsp10, hsp60, and clpp are abundantly expressed in breast cancer tissues rather than adjacent noncancerous tissues. The expression levels of mitochondrial hsp10 and hsp60 were highest in histological grade 3 breast cancer tissues. Additionally, mitochondria with high hsp60 expression were more present in Her2-positive tumors. CONCLUSIONS: We observed that mtUPR was specifically activated in breast cancer tissues but inactivated in normal mammary tissue. MtUPR had also exhibited a particular increase in Her2-overexpression tumors but not in ER- or PR-positive tumors. Taken together, we suggested that mtUPR may act as a potential candidate for developing novel Her2-overexpression breast cancer therapy.
PURPOSE: Mitochondrial unfolding protein are abundant in breast cancer cells, but the mechanism by which breast cancer cells resist apoptosis is still not fully elucidated. In this study, we explored the role of mitochondrial unfolded protein response (mtUPR)-related proteins in four types of breast cancer tissues. METHODS: Mitochondrial fractions were taken from four breast cancer tissues (luminal A, luminal B, Her2 -overexpression, and TNBC) and the expression of mitochondrial polyubiquitinated proteins was observed by western blot and ELISA. In addition, the expression of hsp10, hsp60, and clpp in mitochondria was observed by western blot in breast cancer tissues and adjacent tissues, and confirmed by ELISA. The expression levels of hsp10 and hsp60 were correlated with clinicopathological parameters in 114 breast cancerpatients. RESULTS: We found an increase in the performance of mitochondrial polyubiquitinated proteins in breast cancer tissues of luminal A, luminal B, Her2-overexpression, and TNBC. The mitochondrial hsp10, hsp60, and clpp are abundantly expressed in breast cancer tissues rather than adjacent noncancerous tissues. The expression levels of mitochondrial hsp10 and hsp60 were highest in histological grade 3 breast cancer tissues. Additionally, mitochondria with high hsp60 expression were more present in Her2-positive tumors. CONCLUSIONS: We observed that mtUPR was specifically activated in breast cancer tissues but inactivated in normal mammary tissue. MtUPR had also exhibited a particular increase in Her2-overexpression tumors but not in ER- or PR-positive tumors. Taken together, we suggested that mtUPR may act as a potential candidate for developing novel Her2-overexpression breast cancer therapy.
Entities:
Keywords:
Breast cancer‧mitochondrial unfolded protein response; Her2-overexpression; mtUPR
Authors: Duygu Kuzuoglu-Ozturk; Zhiqiang Hu; Martina Rama; Emily Devericks; Jacob Weiss; Gary G Chiang; Stephen T Worland; Steven E Brenner; Hani Goodarzi; Luke A Gilbert; Davide Ruggero Journal: Cell Rep Date: 2021-06-29 Impact factor: 9.423