A pseudo-meiotic centrosomal function of TEX12 in cancer [article]

Sumit Sandhu, Lucy J Salmon, Jill E Hunter, Caroline L Wilson, Neil D Perkins, Neil Hunter, Owen R Davies, Urszula L McClurg
2019 bioRxiv   pre-print
Cell division by meiosis involves an extraordinary chromosome choreography including pairing, synapsis and crossing over between homologous chromosomes. The many meiosis-specific genes involved in these processes also constitute a latent toolbox of chromosome remodelling and recombination factors that may be exploited through aberrant expression in cancer. Here, we report that TEX12, a structural protein involved in meiotic chromosome synapsis, is aberrantly expressed in human cancers, with
more » ... n cancers, with high TEX12 levels correlating with poor prognosis. We find that TEX12 knock-down causes proliferative failure in multiple cancer cell lines, and confirm its role in the early stages of oncogenesis through murine cancer models. Remarkably, somatically expressed TEX12 localises to centrosomes, leading to altered centrosome number and structure, features associated with cancer development. Further, we identify TEX12 in meiotic centrin-rich bodies, likely precursors of the mitotic centrosome, suggesting that this may represent an additional cellular function of TEX12 in meiosis that has been previously overlooked. Thus, we propose that an otherwise meiotic function of TEX12 in centrosome duplication is responsible for promoting oncogenesis and cellular proliferation in cancer, which may be targeted for novel cancer therapeutics and diagnostics.
doi:10.1101/509869 fatcat:lfsslnic6bfm7b5lbe4cl6t2zu