Pim1 Kinase Inhibitors Exert Anti-Cancer Activity Against HER2-Positive Breast Cancer Cells Through Downregulation of HER2

被引:11
作者
Wang, Bo-Wei [1 ,2 ]
Huang, Chih-Hao [3 ]
Liu, Liang-Chih [3 ]
Cheng, Fang-Ju [1 ,2 ]
Wei, Ya-Ling [1 ,2 ]
Lin, Yueh-Ming [4 ,5 ]
Wang, Yu-Fei [1 ,2 ]
Wei, Ching-Ting [6 ]
Chen, Yeh [7 ]
Chen, Yun-Ju [6 ,8 ]
Huang, Wei-Chien [1 ,2 ,9 ,10 ,11 ,12 ]
机构
[1] China Med Univ, Ctr Mol Med, Grad Inst Biomed Sci, Taichung, Taiwan
[2] China Med Univ, Res Ctr Canc Biol, Taichung, Taiwan
[3] China Med Univ Hosp, Div Breast Surg, Taichung, Taiwan
[4] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Div Colorectal Surg, Kaohsiung, Taiwan
[5] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan
[6] I Shou Univ, Sch Med Int Students, Kaohsiung, Taiwan
[7] China Med Univ, Inst New Drug Dev, Taichung, Taiwan
[8] E Da Hosp, Dept Med Res, Kaohsiung, Taiwan
[9] China Med Univ, Drug Dev Ctr, Taichung, Taiwan
[10] Asia Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan
[11] China Med Univ, PhD Program Canc Biol & Drug Discovery, Taichung, Taiwan
[12] Acad Sinica, Taichung, Taiwan
来源
FRONTIERS IN PHARMACOLOGY | 2021年 / 12卷
关键词
HER2; lapatinib; drug resistance; breast cancer; PIM1; RECEPTOR TYROSINE KINASES; LAPATINIB RESISTANCE; PROSTATE-CANCER; HER2-TARGETED THERAPY; ACQUIRED-RESISTANCE; EGF RECEPTOR; FAMILY; ACTIVATION; MECHANISMS; TRANSCRIPTION;
D O I
10.3389/fphar.2021.614673
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The proviral integration site for moloney murine leukemia virus 1 (Pim1) is a serine/threonine kinase and able to promote cell proliferation, survival and drug resistance. Overexpression of Pim1 has been observed in many cancer types and is associated with the poor prognosis of breast cancer. However, it remains unclear whether Pim1 kinase is a potential therapeutic target for breast cancer patients. In this study, we found that Pim1 expression was strongly associated with HER2 expression and that HER2-overexpressing breast cancer cells were more sensitive to Pim1 inhibitor-induced inhibitions of cell viability and metastatic ability. Mechanistically, Pim1 inhibitor suppressed the expression of HER2 at least in part through transcriptional level. More importantly, Pim1 inhibitor overcame the resistance of breast cancer cells to HER2 tyrosine kinase inhibitor lapatinib. In summary, downregulation of HER2 by targeting Pim1 may be a promising and effective therapeutic approach not only for anti-cancer growth but also for circumventing lapatinib resistance in HER2-positive breast cancer patients.
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页数:11
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