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EMBO Reports

IF: 6.2
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Targeting intratumor heterogeneity suppresses colorectal cancer chemoresistance and metastasis

Published:3 August 2023 DOI: 10.15252/embr.202256416 PMID: 37338390
Shanshan Chao,?Fei Zhang,?Huiwen Yan,?Liuyang Wang,?Liwen Zhang,?Zhi Wang,?Ruixin Xue,?Lei Wang,?Zhenzhen Wu,?Bing Jiang,?Guizhi Shi,?Yuanchao Xue,?Junfeng Du,?Pengcheng Bu

Abstract

Intratumor heterogeneity (ITH) is a barrier to effective therapy. However, it is largely unknown how ITH is established at the onset of tumor progression, such as in colorectal cancer (CRC). Here, we integrate single-cell RNA-seq and functional validation to show that asymmetric division of CRC stem-like cells (CCSC) is critical for early ITH establishment. We find that CCSC-derived xenografts contain seven cell subtypes, including CCSCs, that dynamically change during CRC xenograft progression. Furthermore, three of the subtypes are generated by asymmetric division of CCSCs. They are functionally distinct and appear at the early stage of xenografts. In particular, we identify a chemoresistant and an invasive subtype, and investigate the regulators that control their generation. Finally, we show that targeting the regulators influences cell subtype composition and CRC progression. Our findings demonstrate that asymmetric division of CCSCs contributes to the early establishment of ITH. Targeting asymmetric division may alter ITH and benefit CRC therapy.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Oxaliplatin 61825-94-3 C8H12N2O4Pt 665 suppliers $17.00-$2180.00
Oxaliplatin 61825-94-3 C8H12N2O4Pt 665 suppliers $17.00-$2180.00
Oxaliplatin 61825-94-3 C8H12N2O4Pt 665 suppliers $17.00-$2180.00
Oxaliplatin 61825-94-3 C8H12N2O4Pt 665 suppliers $17.00-$2180.00

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