YAP‐LAMB3 axis dictates cellular resistance of pancreatic ductal adenocarcinoma cells to gemcitabine

• DOI: 10.1002/mc.23785
• Publication Date: 2024-07-17T13:11:28Z
• Authors: Yecheng Li; Xiaolong Wang; Hongpei Yu; Jinming Cao; Jiaming Xie; Jinhong Zhou; Zhenyu Feng; Wei Chen
• Keywords: Hippo signaling pathway

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with poor prognosis and inadequate response to treatment, such as gemcitabine (Gem), first-line chemotherapeutic drug. Understanding molecular determinants that control drug resistance Gem critical predict potentially responsive patients improve benefits therapy. Emerging evidence suggests certain developmental pathways, Hippo signaling, are aberrated play important roles in cancers. Although signaling has been reported a role chemoresistance cancers, it not clarified which specific target gene(s) functionally mediates effect. In present study, we found YAP serves potent barrier for cellular sensitivity PDAC cells Gem. We then identified characterized laminin subunit beta 3 (LAMB3) bona fide YAP-TEAD4 amplify via feedback loop. Such YAP-LAMB3 axis induce epithelial-mesenchymal transition mediate resistance. Taken together, uncovered an regulator Gem, thus providing potential therapeutic targets overcoming PDAC.