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Targeting intratumor heterogeneity suppresses colorectal cancer chemoresistance and metastasis.
Chao, Shanshan; Zhang, Fei; Yan, Huiwen; Wang, Liuyang; Zhang, Liwen; Wang, Zhi; Xue, Ruixin; Wang, Lei; Wu, Zhenzhen; Jiang, Bing; Shi, Guizhi; Xue, Yuanchao; Du, Junfeng; Bu, Pengcheng.
Afiliação
  • Chao S; Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Zhang F; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Yan H; Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Wang L; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Zhang L; Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Wang Z; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA.
  • Xue R; Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Wang L; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Wu Z; Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Jiang B; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Shi G; Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Xue Y; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Du J; Laboratory Animal Research Center, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • Bu P; Key Laboratory of RNA Biology, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
EMBO Rep ; 24(8): e56416, 2023 08 03.
Article em En | MEDLINE | ID: mdl-37338390
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Resistencia a Medicamentos Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: EMBO Rep Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Resistencia a Medicamentos Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: EMBO Rep Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China