Regulation of epithelial-mesenchymal plasticity in pancreatic ductal adenocarcinoma: Role of key molecules in tumor differentiation and therapy

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-06-06 DOI:10.1016/j.ejca.2025.115561

Qi Ling , Meiching Ong , Björn Konukiewitz , Rüdiger Braun , Jens-Uwe Marquardt , Hendrik Lehnert , Holger Kalthoff , Hendrik Ungefroren

{"title":"Regulation of epithelial-mesenchymal plasticity in pancreatic ductal adenocarcinoma: Role of key molecules in tumor differentiation and therapy","authors":"Qi Ling , Meiching Ong , Björn Konukiewitz , Rüdiger Braun , Jens-Uwe Marquardt , Hendrik Lehnert , Holger Kalthoff , Hendrik Ungefroren","doi":"10.1016/j.ejca.2025.115561","DOIUrl":null,"url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with most patients diagnosed at advanced stages. Therefore, understanding tumor development and improving treatment strategies is critical. Tumor cell plasticity enables differentiation, de-differentiation, and trans-differentiation, processes regulated by EMT and MET. These transitions are often controlled by structurally similar but functionally opposing protein pairs, including alternatively spliced isoforms (RAC1/RAC1B or TAp73α/TAp73β), phosphorylated vs. unphosphorylated forms of the same protein (SMAD3), or ligand source (paracrine vs. autocrine TGF-β1). These proteins modulate canonical and non-canonical TGF-β signaling or function as its effectors. This review explores their roles in epithelial signaling and differentiation, aiming to inform novel targeted and personalized PDAC therapies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"225 ","pages":"Article 115561"},"PeriodicalIF":7.6000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804925003430","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with most patients diagnosed at advanced stages. Therefore, understanding tumor development and improving treatment strategies is critical. Tumor cell plasticity enables differentiation, de-differentiation, and trans-differentiation, processes regulated by EMT and MET. These transitions are often controlled by structurally similar but functionally opposing protein pairs, including alternatively spliced isoforms (RAC1/RAC1B or TAp73α/TAp73β), phosphorylated vs. unphosphorylated forms of the same protein (SMAD3), or ligand source (paracrine vs. autocrine TGF-β1). These proteins modulate canonical and non-canonical TGF-β signaling or function as its effectors. This review explores their roles in epithelial signaling and differentiation, aiming to inform novel targeted and personalized PDAC therapies.

查看原文本刊更多论文

胰腺导管腺癌上皮-间充质可塑性调控：关键分子在肿瘤分化和治疗中的作用

胰腺导管腺癌（PDAC）是最致命的癌症之一，大多数患者在晚期被诊断出来。因此，了解肿瘤的发展和改进治疗策略至关重要。肿瘤细胞的可塑性使分化、去分化和反分化成为可能，这些过程由EMT和MET调控。这些转变通常由结构相似但功能相反的蛋白质对控制，包括可选剪接的异构体（RAC1/RAC1B或TAp73α/TAp73β），相同蛋白质的磷酸化形式（SMAD3）或配体来源（旁分泌与自分泌TGF-β1）。这些蛋白调节典型和非典型TGF-β信号或作为其效应物。这篇综述探讨了它们在上皮信号传导和分化中的作用，旨在为新的靶向和个性化PDAC治疗提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.