Inhibitory role of TRIP-Br1 oncoprotein in anticancer drug-mediated programmed cell death via mitophagy activation

Jung, Samil; Myagmarjav, Davaajargal; Jo, Taeyeon; Lee, Soonduk; Han, Songyi; Quynh, Nguyen Thi Ngoc; Anh, Nguyen Hai; Vu, Son Hai; Choi, Yeongseon; Lee, Myeong-Sok

doi:10.7150/ijbs.72138

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Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

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Int J Biol Sci 2022; 18(9):3859-3873. doi:10.7150/ijbs.72138 This issue Cite

Research Paper

Inhibitory role of TRIP-Br1 oncoprotein in anticancer drug-mediated programmed cell death via mitophagy activation

Samil Jung^*, Davaajargal Myagmarjav^*, Taeyeon Jo, Soonduk Lee, Songyi Han, Nguyen Thi Ngoc Quynh, Nguyen Hai Anh, Son Hai Vu, Yeongseon Choi, Myeong-Sok Lee^✉

Division of Biological Sciences, Sookmyung Women's University, Seoul, 14310, South Korea
*These authors have contributed equally to this work.

Citation:

Jung S, Myagmarjav D, Jo T, Lee S, Han S, Quynh NTN, Anh NH, Vu SH, Choi Y, Lee MS. Inhibitory role of TRIP-Br1 oncoprotein in anticancer drug-mediated programmed cell death via mitophagy activation. Int J Biol Sci 2022; 18(9):3859-3873. doi:10.7150/ijbs.72138. https://www.ijbs.com/v18p3859.htm

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Abstract

Chemotherapy has been widely used as a clinical treatment for cancer over the years. However, its effectiveness is limited because of resistance of cancer cells to programmed cell death (PCD) after treatment with anticancer drugs. To elucidate the resistance mechanism, we initially focused on cancer cell-specific mitophagy, an autophagic degradation of damaged mitochondria. This is because mitophagy has been reported to provide cancer cells with high resistance to anticancer drugs. Our data showed that TRIP-Br1 oncoprotein level was greatly increased in the mitochondria of breast cancer cells after treatment with various anticancer drugs including staurosporine (STS), the main focus of this study. STS treatment increased cellular ROS generation in cancer cells, which triggered mitochondrial translocation of TRIP-Br1 from the cytosol via dephosphorylation of TRIP-Br1 by protein phosphatase 2A (PP2A). Up-regulated mitochondrial TRIP-Br1 suppressed cellular ROS levels. In addition, TRIP-Br1 rapidly removed STS-mediated damaged mitochondria by activating mitophagy. It eventually suppressed STS-mediated PCD via degradation of VDACI, TOMM20, and TIMM23 mitochondrial membrane proteins. TRIP-Br1 enhanced mitophagy by increasing expression levels of two crucial lysosomal proteases, cathepsins B and D. In conclusion, TRIP-Br1 can suppress the sensitivity of breast cancer cells to anticancer drugs by activating autophagy/mitophagy, eventually promoting cancer cell survival.

Keywords: Cancer, Mitochondria, Autophagy, Mitophagy, TRIP-Br1

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APA

Jung, S., Myagmarjav, D., Jo, T., Lee, S., Han, S., Quynh, N.T.N., Anh, N.H., Vu, S.H., Choi, Y., Lee, M.S. (2022). Inhibitory role of TRIP-Br1 oncoprotein in anticancer drug-mediated programmed cell death via mitophagy activation. International Journal of Biological Sciences, 18(9), 3859-3873. https://doi.org/10.7150/ijbs.72138.

ACS

Jung, S.; Myagmarjav, D.; Jo, T.; Lee, S.; Han, S.; Quynh, N.T.N.; Anh, N.H.; Vu, S.H.; Choi, Y.; Lee, M.S. Inhibitory role of TRIP-Br1 oncoprotein in anticancer drug-mediated programmed cell death via mitophagy activation. Int. J. Biol. Sci. 2022, 18 (9), 3859-3873. DOI: 10.7150/ijbs.72138.

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CSE

Jung S, Myagmarjav D, Jo T, Lee S, Han S, Quynh NTN, Anh NH, Vu SH, Choi Y, Lee MS. 2022. Inhibitory role of TRIP-Br1 oncoprotein in anticancer drug-mediated programmed cell death via mitophagy activation. Int J Biol Sci. 18(9):3859-3873.

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