RRC ID 76436
Author Oka T, Higa T, Sugahara O, Koga D, Nakayama S, Nakayama KI.
Title Ablation of p57+ Quiescent Cancer Stem Cells Suppresses Recurrence after Chemotherapy of Intestinal Tumors.
Journal Cancer Res
Abstract UNLABELLED:Quiescent cancer stem cells (CSC) are resistant to conventional anticancer treatments and have been shown to contribute to disease relapse after therapy in some cancer types. The identification and characterization of quiescent CSCs could facilitate the development of strategies to target this cell population and block recurrence. Here, we established a syngeneic orthotopic transplantation model in mice based on intestinal cancer organoids to profile quiescent CSCs. Single-cell transcriptomic analysis of the primary tumors formed in vivo revealed that conventional Lgr5high intestinal CSCs comprise both actively and slowly cycling subpopulations, the latter of which specifically expresses the cyclin-dependent kinase inhibitor p57. Tumorigenicity assays and lineage tracing experiments showed that the quiescent p57+ CSCs contribute in only a limited manner to steady-state tumor growth but they are chemotherapy resistant and drive posttherapeutic cancer recurrence. Ablation of p57+ CSCs suppressed intestinal tumor regrowth after chemotherapy. Together, these results shed light on the heterogeneity of intestinal CSCs and reveal p57+ CSCs as a promising therapeutic target for malignant intestinal cancer.
SIGNIFICANCE:A quiescent p57+ subpopulation of intestinal CSCs is resistant to chemotherapy and can be targeted to effectively suppress the recurrence of intestinal cancer.
Volume 83(9)
Pages 1393-1409
Published 2023-5-2
DOI 10.1158/0008-5472.CAN-22-2578
PII 718503
PMID 36880956
MeSH Animals Cell Division Cyclin-Dependent Kinase Inhibitor p57 Intestinal Neoplasms* / pathology Mice Neoplasm Recurrence, Local* / pathology Neoplastic Stem Cells / pathology
IF 9.727
DNA material pcDNA3 Venus-Akaluc (RDB15781)