Translation-dependent establishment of intestinal Cancer Stem Cells

Cells integrate internal and external stimuli by continuously adapting their transcription and translation. tRNAs 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. Cancer stem cells (CSC) are a small population of transformed cell able to sustain tumor growth and responsible for metastasis and drug resistance. The incredible plasticity and genetic heterogeneity of CSC make it extremely difficult to find global markers and/or molecular footprints uniquely expressed by these cells. Here we integrate a combination of unbiased sequencing 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 and associated modification enzymes that operate during Wnt-driven intestinal CSC establishment.