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Effect of pharmacological inhibition of SMYD3 on gene expression in patient-derived CRC-SCs

ABSTRACT: Cancer stem cells (CSC) are responsible for colorectal cancer (CRC) chemoresistance, recurrence, and metastasis. Therefore, it has become crucial finding critical molecular stemness targets that are essential for tumor growth. Here, we performed an extensive in vitro and in vivo molecular and functional characterization revealing the pivotal role of SMYD3 in CSC biology. Specifically, SMYD3 interacts with and methylates c-MYC at K158 and K163, modulating its transcriptional activity implicated in stemness and colorectal malignancy. Together, all the in vitro data collected, suggest that SMYD3 pharmacological inhibition affects clonogenic and self-renewal potential of patient-derived CRC-SCs and organoids by altering their molecular signature. Moreover, we showed that SMYD3 stable knock-out or its pharmacological inhibition drastically reduced CRC tumorigenicity in vivo, and reduced the metastatic potential of CRC-SCs. Thus, our findings identify SMYD3 as a promising therapeutic target, acting directly on c-MYC, with potential implications for countering CRC-SCs proliferation, chemoresistance, and metastatic dissemination.

ORGANISM(S): Homo sapiens

PROVIDER: GSE264227 | GEO | 2025/06/17

REPOSITORIES: GEO

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