Transcriptional hallmarks of cancer cell lines reveal an emerging role of branched chain amino acid catabolism.

Abstract

A comparative analysis between cancer cell lines and healthy dividing cells was performed using data (289 microarrays and 50 RNA-seq samples) from 100 different cancer cell lines and 6 types of healthy stem cells. The analysis revealed two large-scale transcriptional events that characterize cancer cell lines. The first event was a large-scale up-regulation pattern associated to epithelial-mesenchymal transition, putatively driven by the interplay of the SP1 transcription factor and the canonical Wnt signaling pathway; the second event was the failure to overexpress a diverse set of genes coding membrane and extracellular proteins. This failure is putatively caused by a lack of activity of the AP-1 complex. It was also shown that the epithelial-mesenchymal transition was associated with the up-regulation of 5 enzymes involved in the degradation of branched chain amino acids. The suitability of silencing one of this enzymes (branched chain amino acid transaminase 2; BCAT2) with therapeutic effects was tested experimentally on the breast cancer cell line MCF-7 and primary cell culture of breast tumor (BCC), leading to lower cell proliferation. The silencing of BCAT2 did not have any significant effect on ASM and MCF10A cells, which were used as models of healthy dividing cells.