A new study from Fleming researchers published in Oncogene identifies a novel link between heat induced stress signals and alternative splicing regulation in gastric cancer.
Alternative Splicing (AS) is highly altered in cancers of all types. This results in the generation of isoforms that facilitate tumour progression by altering cancer cell traits, or even determine the response to cancer therapeutic approaches. In response to oncogenic signals, AS regulators such as the Serine-Arginine rich proteins (SR) and the heterogeneous nuclear Ribonucleoproteins (hnRNP) show altered expression levels, subnuclear distribution and/or post-translational modification status, thus driving AS outcome. However, the link(s) between extracellular signals and AS changes remains largely unexplored.
In a new study published in Oncogene, entitled “The scaffold protein IQGAP1 links heat-induced stress signals to alternative splicing regulation in gastric cancer cells”, Kafasla and colleagues report that a scaffold protein, IQGAP1, known for its cytoplasmic role, performs this task in response to heat-induced signals. They show that in gastric cancer cells, a nuclear pool of IQGAP1 acts as a tethering module for a group of spliceosome components, including hnRNPM, a splicing factor critical for the response of the spliceosome to heat-shock. Nuclear IQGAP1 is necessary for the response of the splicing machinery to heat-induced signals.
Moreover, genome-wide analyses reveal that IQGAP1 and hnRNPM co-regulate the AS of a cell cycle-related RNA regulon in gastric cancer cells, thus favouring the accelerated proliferation phenotype of gastric cancer cells, as proved by in vitro and in vivo experiments presented in this study.
DOI: 10.1038/s41388-021-01963-7