Data from YAP and AP-1 Cooperate to Initiate Pancreatic Cancer Development from Ductal Cells in Mice

• DOI: 10.1158/0008-5472.c.6512139.v1
• Publication Date: 2023-03-31T06:01:37Z
• Authors: Jaeoh Park; David Eisenbarth; Wonyoung Choi; Hail Kim; Chan Choi; Dahye Lee; Dae-Sik Lim
• Keywords: Hippo signaling pathway; Ductal cells

<div>Abstract<p>The development of pancreatic cancer is heavily dependent upon the aberrant activation KRAS signaling. Among downstream targets KRAS, effectors Hippo pathway YAP and TAZ (YAP/TAZ) are crucial during initiation progression. However, little known about cell type-specific effects YAP/TAZ on cancer. Here we clarify unique consequences in ductal population pancreas by generating mice with duct cell-specific, inducible knockouts <i>Lats1</i> <i>Lats2</i>, main kinases upstream YAP/TAZ. Oncogenic deletion <i>Lats1/2</i> cells led to rapid transformation pancreas, which was accompanied a robust increase expression AP-1 target genes. Pharmacologic inhibition activity induced death knockout organoids attenuated YAP-dependent <i>in vivo</i>. Both were activated KRAS-dependent human patients adenocarcinoma, suggesting that this signaling hub represents an important mediator Collectively, these data define mechanism suggest can suppress development.</p>Significance:<p>A cell-specific mouse model featuring constitutively active allows for study screening pharmacologically inhibitors.</p></div>