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

Autor: Li Y; Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China., Wang X; Department of General Surgery, Haian People's Hospital, Haian, China., Yu H; General Surgery Department, Taizhou Second People's Hospital, Taizhou, China., Cao J; Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China., Xie J; Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China., Zhou J; General Surgery Department, Taizhou Second People's Hospital, Taizhou, China., Feng Z; Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China., Chen W; Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2024 Oct; Vol. 63 (10), pp. 1953-1966. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1002/mc.23785
Abstrakt: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with poor prognosis and inadequate response to treatment, such as gemcitabine (Gem), the first-line chemotherapeutic drug. Understanding the molecular determinants that control drug resistance to Gem is critical to predict potentially responsive patients and improve the benefits of Gem therapy. Emerging evidence suggests that certain developmental pathways, such as Hippo signaling, are aberrated and play important roles in Gem resistance in cancers. Although Hippo signaling has been reported to play a role in chemoresistance in cancers, it has not been clarified which specific target gene(s) functionally mediates the effect. In the present study, we found that YAP serves as a potent barrier for the cellular sensitivity of PDAC cells to Gem. We then identified and characterized laminin subunit beta 3 (LAMB3) as a bona fide target of YAP-TEAD4 to amplify YAP signaling via a feedback loop. Such a YAP-LAMB3 axis is critical to induce epithelial-mesenchymal transition and mediate Gem resistance. Taken together, we uncovered that YAP-LAMB3 axis is an important regulator of Gem, thus providing potential therapeutic targets for overcoming Gem resistance in PDAC.
(© 2024 The Author(s). Molecular Carcinogenesis published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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