Abstract
IntroductionMetastasis is the main cause of cancer mortality. However, the triggering mechanisms and regulation of epithelial–mesenchymal transition (EMT) factors in the commitment of metastasis have not been well characterised. Spermatogenic Zip 1 (SPZ1) acts as a proto-oncogene and an upstream regulator of EMT during tumorigenesis.Material and methodsHere we reported that acetyltransferase Tip60 (HIV-1 Tat-interacting protein 60 kDa) mediates acetylation of SPZ1 on lysine residues at positions 369 and 374 and TWIST1 on lysine residues at positions 73 and 76, which are required for of SPZ1-TWIST1 complex formation and cancer cell migration in vitro and in vivo.Results and discussionsEctopic SPZ1 and TWIST1 expression, but not that of TWIST1 alone, enhanced vascular endothelial growth factor (VEGF) expression via recruitment of bromodomain-containing protein 4 (BRD4), enhancing RNA Pol II-dependent transcription for inducing metastasis. Neutralisation of VEGF by humanised monoclonal antibodies, such as avastin, effectively abrogates EMT and oncogenesis induced by acetylated SPZ1–TWIST1 complex.ConclusionOur finding highlights the importance of acetylation signalling of the SPZ1–TWIST1–BRD4 axis in mediating EMT and its regulation on tumour initiation and metastasis.
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