Nuclear IQGAP1 promotes gastric cancer cell growth by altering the splicing of a cell-cycle regulon in co-operation with hnRNPM

Heterogeneous nuclear ribonucleoproteins (hnRNPs) play crucial roles in alternative splicing, regulating the cell proteome. When they are miss-expressed, they contribute to human diseases. hnRNPs are nuclear proteins, but where they localize and what determines their tethering to nuclear assemblies in response to signals remain open questions. Here we report that IQGAP1, a cytosolic scaffold protein, localizes in the nucleus of gastric cancer cells acting as a tethering module for hnRNPM and other spliceosome components. One of the consequences of the IQGAP1-hnRNPM interaction is to change the alternative splicing of the anaphase promoting complex (ANAPC), subunit 10 and is required for the hnRNPM response to heat-induced stress signals. Together, IQGAP1 and hnRNPM promote gastric cancer cell growth, and their genetic depletion leads to cell cycle arrest and halts tumour progression. We propose that in response to stress-signals IQGAP1 translocates in the nucleus to coordinate gastric tumour growth by recruiting spliceosome components that drive cell cycle progression.