Tailoring a novel colorectal cancer stem cell-targeted therapy by inhibiting the SMYD3/c-MYC axis.

ABSTRACT: Cancer stem cells (CSCs) are responsible for colorectal cancer (CRC) chemoresistance, recurrence, and metastasis. Therefore, identifying molecular stemness targets that are involved in tumor growth is crucial for effective treatment. Here, we performed an extensive in vitro and in vivo molecular and functional characterization, revealing the pivotal role of the lysine methyltransferase SET and MYND Domain Containing 3 (SMYD3) in colorectal cancer stem cell (CRC-SC) biology. Specifically, we showed that SMYD3 interacts with and methylates c-MYC at K158 and K163, thereby modulating its transcriptional activity, which is implicated in stemness and colorectal malignancy. Our in vitro data suggest that SMYD3 pharmacological inhibition or its stable genetic ablation affects the clonogenic and se

SUBMITTER: Lepore Signorile M 

PROVIDER: S-EPMC12209437 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature