Translation-dependent establishment of intestinal Cancer Stem Cells

Cells integrate internal and external stimuli by continuously adapting their transcription and translation. One of the main players involved in the latter are tRNAs, which are heterogeneous and highly modified molecules necessary to correctly translate mRNAs into proteins. Even though their discovery goes back to the late 50s, it is only in the last years that their active role in regulating translation has started to be highlighted both in health and disease. In particular, tRNA modifications have been recently linked with cancer initiation, invasion and resistance to therapy. Cancer Stem Cells (CSCs) are a small population of transformed cells able to sustain tumor growth and responsible for metastasis and drug resistance. However, the incredible plasticity and genetic heterogeneity of CSCs make it extremely difficult to find global markers and/or molecular footprints uniquely expressed by these cells. Here, we integrate a combination of multi-omics approaches to identify, in the intestine, the specific translational dynamics promoted by Wnt-driven transformation in stem cells. Through this multilayer approach, we describe the existence of distinct tRNAs, tRNA modifications and tRNA-modifying enzymes involved in the Wnt-dependent establishment of intestinal CSCs.