Beyond just a tight fortress: contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer.
Beyond just a tight fortress: contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer.
复制标题
不仅仅是一个坚固的堡垒：间质在胰腺癌上皮-间充质转化中的作用。
DOI：
10.1038/s41392-020-00341-1
复制
发表时间：
2020-10-30
影响因子：
39.3
通讯作者：
Lim KH
中科院分区：
文献类型：
--
作者：
Bulle A;Lim KH
胰腺导管腺癌(PDAC)患者迫切需要新的有效治疗方法。针对驱动器突变的治疗方法，特别是KRAS癌蛋白及其效应级联，一直是无效的。越来越清楚的是，PDAC广泛的纤维炎症间质(或间质增生)在PDAC的进展和治疗耐药中起着积极的作用。促结缔组织间质由致密的细胞外基质(ECM)组成，主要由肿瘤相关成纤维细胞(CAF)沉积，并渗入各种类型的免疫细胞。致密的ECM起到了物理屏障的作用，限制了肿瘤血管和治疗药物对PDAC细胞的分布。此外，越来越多的证据表明，CAF和ECM都通过多种机制促进PDAC细胞的侵袭性，特别是参与上皮-间充质转化(EMT)计划。间充质样表型的获得使PDAC细胞更具侵袭性，并对治疗诱导的凋亡具有抵抗力。在这里，我们批判性地回顾了关于每个基质元素促进PDAC中EMT的信号机制的开创性文章和最近的文章。我们讨论了目前使用的最适合研究PDAC中EMT的实验模型，这些模型有助于增加成功临床翻译的机会。
Novel effective treatment is direly needed for patients with pancreatic ductal adenocarcinoma (PDAC). Therapeutics that target the driver mutations, especially the KRAS oncoprotein and its effector cascades, have been ineffective. It is increasing clear that the extensive fibro-inflammatory stroma (or desmoplasia) of PDAC plays an active role in the progression and therapeutic resistance of PDAC. The desmoplastic stroma is composed of dense extracellular matrix (ECM) deposited mainly by the cancer-associated-fibroblasts (CAFs) and infiltrated with various types of immune cells. The dense ECM functions as a physical barrier that limits tumor vasculatures and distribution of therapeutics to PDAC cells. In addition, mounting evidence have demonstrated that both CAFs and ECM promote PDAC cells aggressiveness through multiple mechanisms, particularly engagement of the epithelial-mesenchymal transition (EMT) program. Acquisition of a mesenchymal-like phenotype renders PDAC cells more invasive and resistant to therapy-induced apoptosis. Here, we critically review seminal and recent articles on the signaling mechanisms by which each stromal element promotes EMT in PDAC. We discussed the experimental models that are currently employed and best suited to study EMT in PDAC, which are instrumental in increasing the chance of successful clinical translation.
登录
查看更多内容
影响因子：
--
作者：
Cho Y;Lee HW;Kang HG;Kim HY;Kim SJ;Chun KH
通讯作者：
Chun KH
影响因子：
15.9
作者：
Collins, Meredith A.;Bednar, Filip;di Magliano, Marina Pasca
通讯作者：
di Magliano, Marina Pasca
影响因子：
10.5
作者：
Ancrile, Brooke;Lim, Kian-Huat;Counter, Christopher M.
通讯作者：
Counter, Christopher M.
影响因子：
10.5
作者：
D'Amico S;Shi J;Martin BL;Crawford HC;Petrenko O;Reich NC
通讯作者：
Reich NC
影响因子：
64.5
作者：
David CJ;Huang YH;Chen M;Su J;Zou Y;Bardeesy N;Iacobuzio-Donahue CA;Massagué J
通讯作者：
Massagué J