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Constitutive BAK/MCL1 complexes predict paclitaxel and S63845 sensitivity of ovarian cancer

文献类型：期刊论文

作者Liu, Dongyan1,2,3; Hou, Xiaonan4; Wu, Wangyu5; Zafagnin, Valentina4; Li, Yunjian2,6; Correia, Cristina7,8; Zhao, Zhiyang1,2,3; Zhao, Chenggang1,2,3; Liu, Zhirong1,2; Zhang, Tao5
刊名CELL DEATH & DISEASE
出版日期2021-08-12
卷号12
ISSN号2041-4889
DOI10.1038/s41419-021-04073-0
通讯作者Kaufmann, Scott H.(Kaufmann.Scott@mayo.edu) ; Dai, Haiming(Daih@cmpt.ac.cn)
英文摘要We previously found that preformed complexes of BAK with antiapoptotic BCL2 proteins predict BH3 mimetic sensitivities in lymphohematopoietic cells. These complexes have not previously been examined in solid tumors or in the context of conventional anticancer drugs. Here we show the relative amount of BAK found in preformed complexes with MCL1 or BCLXL varies across ovarian cancer cell lines and patient-derived xenografts (PDXs). Cells bearing BAK/MCL1 complexes were more sensitive to paclitaxel and the MCL1 antagonist S63845. Likewise, PDX models with BAK/MCL1 complexes were more likely to respond to paclitaxel. Mechanistically, BIM induced by low paclitaxel concentrations interacted preferentially with MCL1 and displaced MCL1-bound BAK. Further studies indicated that cells with preformed BAK/MCL1 complexes were sensitive to the paclitaxel/S63845 combination, while cells without BAK/MCL1 complexes were not. Our study suggested that the assessment of BAK/MCL1 complexes might be useful for predicting response to paclitaxel alone or in combination with BH3 mimetics.
WOS关键词PRECISION MEDICINE ; BIM ; APOPTOSIS ; CHEMOTHERAPY ; BAK ; PARP ; MITOCHONDRIA ; COMBINATION ; ACTIVATION ; RESISTANCE
资助项目National Natural Science Foundation of China[81572948] ; National Natural Science Foundation of China[21772201] ; National Natural Science Foundation of China[31970701] ; Anhui Medical University[LHJJ202006] ; Anhui Medical University[LHJJ202007] ; U.S. National Institutes of Health[P50 CA136393] ; Center of Medical Physics and Technology[LHJJ202006] ; Center of Medical Physics and Technology[LHJJ202007]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000685343900002
出版者SPRINGERNATURE
资助机构National Natural Science Foundation of China ; Anhui Medical University ; U.S. National Institutes of Health ; Center of Medical Physics and Technology
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/124395]  
专题中国科学院合肥物质科学研究院
通讯作者Kaufmann, Scott H.; Dai, Haiming
作者单位1.Chinese Acad Sci, Hefei Canc Hosp, Hefei 230031, Peoples R China
2.Chinese Acad Sci, Hefei Inst Phys Sci, Inst Hlth & Med Technol, Anhui Prov Key Lab Med Phys & Technol, Hefei 230031, Peoples R China
3.Univ Sci & Technol China, Hefei 230026, Peoples R China
4.Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA
5.Anhui Med Univ, Affiliated Hosp 2, Hefei 230601, Peoples R China
6.Anhui Med Univ, Sch Basic Med Sci, Hefei 230032, Peoples R China
7.Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA
8.Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA
推荐引用方式
GB/T 7714		 Liu, Dongyan,Hou, Xiaonan,Wu, Wangyu,et al. Constitutive BAK/MCL1 complexes predict paclitaxel and S63845 sensitivity of ovarian cancer[J]. CELL DEATH & DISEASE,2021,12.
APA Liu, Dongyan.,Hou, Xiaonan.,Wu, Wangyu.,Zafagnin, Valentina.,Li, Yunjian.,...&Dai, Haiming.(2021).Constitutive BAK/MCL1 complexes predict paclitaxel and S63845 sensitivity of ovarian cancer.CELL DEATH & DISEASE,12.
MLA Liu, Dongyan,et al."Constitutive BAK/MCL1 complexes predict paclitaxel and S63845 sensitivity of ovarian cancer".CELL DEATH & DISEASE 12(2021).

入库方式： OAI收割

来源：合肥物质科学研究院

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