L3MBTL3 and active STAT3 collaboratively up-regulate SNAIL transcription to promote metastasis in breast cancer

Abstract Active STAT3 pathway promotes epithelial mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of epithelial mesenchymal transition key transcription factor SNAIL through DNA-binding independent way. However, the mechanism that how is STAT3 recruited to SNAIL promoter to upregulate transcription in DNA independent way is still unclear. In our study, we found a lysine methylated binding protein L3MBTL3 was positively associated with metastatic and poor prognosis in breast cancer. L3MBTL3 also promoted epithelial-mesenchymal transition, migration, invasion and metastasis in breast cancer. Mechanism analysis found L3MBTL3 interacted with active STAT3 and recruited active STAT3 on SNAIL promoter to up-regulated SNAIL transcription. The interaction between L3MBTL3 and active STAT3 was required for SNAIL transcription up-regulation, migration and invasion in breast cancer, while the methylated lysine binding activity of L3MBTL3 is not required for these functions. In conclusion, L3MBTL3 and active STAT3 collaboratively up-regulate SNAIL transcription to promote breast cancer metastasis.