ZNF37A promotes tumor metastasis through transcriptional control of THSD4-TGF-b axis in colorectal cancer

We showed that ZNF37A, a member of KRAB-ZFP family, was upregulated in poorly differentiated CRC patients, and associated with tumor metastasis. ZNF37A elevated the invasive properties of multiple CRC cellular models and promoted distal metastasis in orthotopic mouse model. Further investigation revealed that metastasis event is attributed to elevated extracellular TGF-b level and activated cancer-associated fibroblasts (CAFs) in TME rewired by ZNF37A overexpression. Mechanistically, ZNF37A bound to the promoter of the TME modulator THSD4 to suppress its transcription through recruiting KAP1, which is required for ZNF37A-mediated TGF-b activation and CRC metastasis. In conclusion, our study indicates ZNF37A promotes TGF-b signaling in CRC cells and activates CAFs by repressing THSD4 transcription, suggesting ZNF37A may drive CRC metastasis, as well serve as a predictive biomarker for CRC progression.