Fig. 5

Schematic illustration of the proposed mechanism behind mitigation of sunitinib-induced disruption of sarcomere by inhibition of the Hippo pathway (A) Stimulation with sunitinib causes reduction of nuclear localization of YAP1 as well as disruption of sarcomere in iPSC-CM probably through activation of the Hippo pathway. (B) Washout of sunitinib normalizes the activated status of the Hippo pathway and the extent of nuclear localization of YAP1 as well as sarcomere disruption returns to normal level possibly as a result of sarcomere synthesis. (C) XMU-MP-1 is considered to mimic the condition of sunitinib washout as it is an inhibitor of kinase MST1/2. Indeed, XMU-MP-1 suppressed the sunitinib-induced disruption of sarcomere