Cancer-specific association between Tau (MAPT) and cellular pathways, clinical outcome, and drug response

Abstract

AbstractTau (MAPT) is a microtubule-associated protein causing common neurodegenerative diseases or inherited frontotemporal lobar degenerations. Emerging evidence for non-canonical functions of Tau in DNA repair and P53 regulation suggests its involvement in cancer. Indeed, preliminary studies have correlated Tau expression with cancer survival or response to therapies. To bring new evidence for a relevant role of Tau in cancer, we carried out anin silicopan-cancer analysis ofMAPTtranscriptomic profile in over 10000 clinical samples from 32 cancer types and over 1300 pre-clinical samples from 28 cancer types provided by the TCGA and the DEPMAP datasets respectively.MAPTexpression associated with key cancer hallmarks including inflammation, proliferation, and epithelial to mesenchymal transition, showing cancer-specific patterns. In some cancer types,MAPTfunctional networks were affected by P53 mutational status. We identified new associations ofMAPTwith clinical outcomes and drug response in a context-specific manner. Overall, our findings indicate that theMAPTgene is a potential major player in multiple types of cancer. Importantly, the impact of Tau on cancer seems to be heavily influenced by the specific cellular environment.