Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells

被引：111

作者：

Colak, S. ^{[1
]}

Zimberlin, C. D. ^{[1
]}

Fessler, E. ^{[1
]}

Hogdal, L. ^{[2
]}

Prasetyanti, P. R. ^{[1
]}

Grandela, C. M. ^{[1
]}

Letai, A. ^{[2
]}

Medema, J. P. ^{[1
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Ctr Expt Mol Med, LEXOR Lab Expt Oncol & Radiobiol, NL-1105 AZ Amsterdam, Netherlands

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

来源：

CELL DEATH AND DIFFERENTIATION | 2014年 / 21卷 / 07期

关键词：

PLUS IRINOTECAN; BCL-2; INHIBITOR; APOPTOSIS; ABT-199; BAX; TRANSLOCATION; NAVITOCLAX; ABT-737; DEATH;

D O I：

10.1038/cdd.2014.37

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Tumor heterogeneity is in part determined by the existence of cancer stem cells (CSCs) and more differentiated tumor cells. CSCs are considered to be the tumorigenic root of cancers and suggested to be chemotherapy resistant. Here we exploited an assay that allowed us to measure chemotherapy-induced cell death in CSCs and differentiated tumor cells simultaneously. This confirmed that CSCs are selectively resistant to conventional chemotherapy, which we revealed is determined by decreased mitochondrial priming. In agreement, lowering the anti-apoptotic threshold using ABT-737 and WEHI-539 was sufficient to enhance chemotherapy efficacy, whereas ABT-199 failed to sensitize CSCs. Our data therefore point to a crucial role of BCLXL in protecting CSCs from chemotherapy and suggest that BH3 mimetics, in combination with chemotherapy, can be an efficient way to target chemotherapy-resistant CSCs.

引用

页码：1170 / 1177

页数：8

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