Graphical Abstract Highlights d METTL13 is the physiologic eEF1A lysine 55 dimethyltransferase d METTL13 dimethylation of eEF1A stimulates protein synthesis in cancer cells d The METTL13-eEF1A methylation axis fuels Ras-driven tumorigenesis in vivo d METTL13 depletion sensitizes cancer cells to PI3K and mTOR pathway inhibitors

Highlights d SETD5 is an epigenetic driver of pancreatic cancer resistance to MEK1/2 inhibition d SETD5 has no intrinsic methylation activity on histones, including at H3 lysine 36 d A SETD5 co-repressor complex regulates a network of drug resistance pathways d Co-targeting of MEK1/2 and the SETD5 complex results in sustained tumor inhibition

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Although many examples of simulated and real microgravity demonstrating their profound effect on biological systems are described in literature, few reports deal with hypergravity and vibration effects, the levels of which are severely increased during the launch preceding the desired microgravity period. Here, we used planarians, flatworms that can regenerate any body part in a few days. Planarians are an ideal model to study the impact of launch-related hypergravity and vibration during a regenerative process in a “whole animal” context. Therefore, planarians were subjected to 8.5 minutes of 4 g hypergravity (i.e. a human-rated launch level) in the Large Diameter Centrifuge (LDC) and/or to vibrations (20–2000 Hz, 11.3 Grms) simulating the conditions of a standard rocket launch. The transcriptional levels of genes (erg-1, runt-1, fos, jnk, and yki) related with the early stress response were quantified through qPCR. The results show that early response genes are severely deregulated after static and dynamic loads but more so after a combined exposure of dynamic (vibration) and static (hypergravity) loads, more closely simulating real launch exposure profiles. Importantly, at least four days after the exposure, the transcriptional levels of those genes are still deregulated. Our results highlight the deep impact that short exposures to hypergravity and vibration have in organisms, and thus the implications that space flight launch could have. These phenomena should be taken into account when planning for well-controlled microgravity studies.