A groundbreaking study published in Signal Transduction and Targeted Therapy, a high-impact journal within the prestigious Nature Portfolio and featuring the contribution from ISOF researchers, has identified the lysine methyltransferase SMYD3 as a critical regulator of colorectal cancer stem cells, which drive chemoresistance, recurrence, and metastasis.
Researchers demonstrated that SMYD3 directly methylates the oncoprotein c-MYC at residues K158 and K163, amplifying its transcriptional control over stemness and malignancy pathways.
Both pharmacological inhibition and genetic ablation of SMYD3 disrupted colorectal cancer stem cells clonogenic and self-renewal capabilities in patient-derived organoids and models. Crucially, SMYD3 suppression drastically reduced tumorigenicity in vivo and blocked metastatic dissemination. These findings position SMYD3 as a promising therapeutic target to combat CRC progression by dismantling c-MYC-dependent CSC maintenance.
The study underscores SMYD3’s pivotal role in colorectal cancer stem cells biology, offering a strategic approach to halt metastasis and overcome treatment resistance. Future therapies targeting this axis could significantly improve outcomes for aggressive colorectal cancer.
https://doi.org/10.1038/s41392-025-02290-z
