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Pharmacologic inhibition of AP-1 activity induced demise in Lats1/2 knockout organoids and attenuated YAP-dependent transformation of the pancreas in vivo. Both YAP and AP-1 were activated throughout the growth of KRAS-dependent cancer in mice and human patients with pancreatic ductal adenocarcinoma, suggesting that this signaling hub signifies a significant mediator of pancreatic disease development and progression. Collectively, these data define a YAP-de