Year: 2019
Type: article
Abstract: Chemoresistance in cancer is linked to a subset of cancer cells termed "cancer stem cells" (CSCs), and in particular, those expressing the CD44 variant appear to represent a more aggressive disease phenotype. Herein, we demonstrate that CD44v6 represents a CSC population with increased resistance to chemotherapeutic agents, and its high expression is frequently associated with poor overall survival (OS) and disease-free survival (DFS) in patients with colorectal cancer (CRC). CD44v6+ cells showed elevated resistance to chemotherapeutic drugs and significantly high tumor initiation capacity. Inhibition of CD44v6 resulted in the attenuation of self-renewal capacity and resensitization to chemotherapeutic agents. Of note, miRNA profiling of CD44v6+ spheroid-derived CSCs identified a unique panel of miRNAs indicative of high self-renewal capacity. In particular, miR-1246 was overexpressed in CD44v6+ cells, and associated with poor OS and DFS in CRC patients. We demonstrate that CD44v6+ CSCs induced chemoresistance and enhance tumorigenicity in CRC cells, and this was in part orchestrated by a distinct panel of miRNAs with dysregulated profiles. These findings suggest that specific miRNAs could serve as therapeutic targets as well as promising prognostic biomarkers in patients with colorectal neoplasia.
Source: JCI Insight
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: G251590960, G3173870227, Development of microRNA Biomarkers For Noninvasive Detection of Colorectal Cancer, G3411000325, G3695502894, G4144402113, G4300560175, G6681643532, Next Generation Sequencing-Based Approaches for the Development of Epigenetic Biomarkers for Predicting Therapeutic Outcome in Patients With Colorectal Cancer, Aspirin and Cancer Prevention in Lynch Syndrome: From Cell to Population Data, G9000016337, G9000182627, G9000208368, G9000226584, G9000318416
OpenAlex ID: W2923635845