YTHDF1 targets the chemotherapy response by suppressing NOTCH1-induced stemness in colorectal cancer.

ABSTRACT: N⁶-methyladenosine (m⁶A) modification of mRNAs is a predominant epigenetic regulatory mechanism in tumor initiation and progression. Cancer stem cells (CSCs) are the key drivers of colorectal cancer (CRC) initiation and chemotherapy resistance. Here, we found that the m⁶A reader YT521-B homologous domain family, member 1 (YTHDF1), promotes CRC stemness, tumorigenesis, and chemotherapy resistance. YTHDF1 protein expression was positively correlated with CD133 and LGR5 expression in human CRC tissues (N = 184, P < 0.001 for both markers). YTHDF1 promoted m⁶A-dependent self-renewal in CSCs and patient-derived organoids and increased the tumor-initiating potential in vivo. Lgr5-specific Ythdf1-KI mice presented accelerated Apc^Min/+ (P < 0.

SUBMITTER: Cheung H 

PROVIDER: S-EPMC12719390 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature