首页|Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy
Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NSTL
Colorectal cancer (CRC) patient-derived organoids predict responses to chemotherapy. Here we used them to investigate relapse after treatment. Patient-derived organoids expand from highly proliferative LGR5+ tumor cells; however, we discovered that lack of optimal growth conditions specifies a latent LGR5+ cell state. This cell population expressed the gene MEX3A, is chemoresistant and regenerated the organoid culture after treatment. In CRC mouse models, Mex3a+ cells contributed marginally to metastatic outgrowth; however, after chemotherapy, Mex3a+ cells produced large cell clones that regenerated the disease. Lineage-tracing analysis showed that persister Mex3a+ cells downregulate the WNT/stem cell gene program immediately after chemotherapy and adopt a transient state reminiscent to that of YAP+ fetal intestinal progenitors. In contrast, Mex3a-deficient cells differentiated toward a goblet cell-like phenotype and were unable to resist chemotherapy. Our findings reveal that adaptation of cancer stem cells to suboptimal niche environments protects them from chemotherapy and identify a candidate cell of origin of relapse after treatment in CRC.
Adrian Alvarez-Varela、Laura Novellasdemunt、Francisco M. Barriga、Xavier Herno-Momblona、Adria Canellas-Socias、Marta Sevillano、Carme Cortina、Diana Stork、Clara Morral、Gemma Turon、Felipe Slebe、Laura Jimenez-Gracia、Ginevra Caratu、Peter Jung、Giorgio Stassi、Holger Heyn、Daniele V. F. Tauriello、Camille Stephan-Otto Attolin、Eduard Batlle、Sara Cano-Crespo、Lidia Mateo、Sabine Tejpar、Elena Sancho
展开 >
Institute for Research 'in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and
NSTL
