期刊
CELL CYCLE
卷 15, 期 12, 页码 1531-1537出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/15384101.2014.973321
关键词
apoptosis; ABT-737; BCLXL; colorectal cancer; cancer stem cell; chemotherapy; fibroblast; microenvironment; resistance
类别
资金
- Netherlands Organization for Scientific Research (NWO
- Gravitation-Cancer Genomics Center The Netherlands Zwaartekracht)
- Dutch Cancer Society [UVA2009-4416, UVA2012-5735]
- MLDS [FP13-07]
- Alpe dHuzes/KWF (CONNECTION)
There is increasing evidence that cancers are heterogeneous and contain a hierarchical organization consisting of cancer stem cells and their differentiated cell progeny. These cancer stem cells are at the core of the tumor as they represent the clonogenic cells within a tumor. Moreover, these cells are considered to contain selective therapy resistance, which suggests a pivotal role in therapy resistance and tumor relapse. Here we show that differentiated cells can re-acquire stemness through factors secreted from fibroblasts. This induced CSC state also coincides with re-acquisition of resistance to chemotherapy. Resistance induced in newly formed CSCs is mediated by the anti-apoptotic molecule BCLXL and inhibition of BCLXL with the BH3 mimetic ABT-737 sensitizes these cancer cells toward chemotherapy. These data point to an important interplay between tumor cells and their microenvironment in the regulation of stemness and therapy resistance.
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