fig1

Figure 1. Schematic representation of the main mechanism of resistance to SINE compounds. Increased expression of NRG1 and ERBB3 contributes to SINE resistance by increasing cell survival, migration, and proliferation. Increased expression of MAGE-A reduces apoptosis, fostering resistance to SINE. Downregulation of WNT10A, DUSP1, and ETCV7 reduces SINE effectiveness. Reduction in ferroptosis also contributes to SINE resistance. Increased expression of HNRNPU, by modulating ribosome activity, increases resistance to SINE. For detailed explanations of SINE mechanisms of resistance, see the main text. SINE: Selective inhibitors of nuclear export; NRG1: neuroregulin 1; ERBB3: Erb-B2 receptor tyrosine kinase 3; MAGE-A: melanoma antigen family A; HNRNPU: heterogeneous nuclear ribonucleoprotein U; IkBa: nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; NFκB: nuclear factor kappa-B; XPO1: exportin 1; hnRNPU: heterogeneous nuclear ribonucleprotein U; Pol II: RNA polymerase II; BIM: Bcl-2 interacting mediator of cell death.