Jumping genes are repetitive sequences able to copy themselves to new genomic locations. The long interspersed nuclear element 1 (L1) is the only autonomous jumping gene in the human genome (1). Due to the potential deleterious effect of their mobilisation, L1s are repressed in most circumstances (2). Yet, L1s are active in embryonic development and in epithelial cancers (1, 3).
The hallmark of an aggressive epithelial tumour is its ability to metastasise, i.e. to migrate to other parts of the body. The mechanism that enables this migration is the Epithelial to Mesenchymal Transition (EMT) (4). EMT is triggered by signalling pathways such as TGF-B, Notch and Wnt, that activate a network of transcription factors that act as both repressors of epithelial genes and activators of mesenchymal genes (5).
As EMT and L1 activation take place in the same context. We hypothesise that EMT activates L1 retrotransposition.
Analysis of RNA-seq expression data from 200 tumour samples (The Cancer Genome Atlas Project) shows that genes involved in EMT correlate positively with L1 activity associated genes, gene set enrichment score FDR q-val= 0.004. Furthermore, qRT-PCR measuring L1 mRNA levels before and after EMT induction shows a significant increase in L1 mRNA abundance after in vitro EMT induction.
Our data strongly suggests that induction of EMT activates L1 transcription.
Further research is needed to fully clarify the role of jumping genes in cancer progression: is their activation a by-product of EMT or is it required for EMT to proceed?