IRE1 is a promising therapeutic target in pancreatic cancer.

IF 5 2区生物学 Q2 CELL BIOLOGY

American journal of physiology. Cell physiology Pub Date : 2025-03-01 Epub Date: 2025-01-16 DOI:10.1152/ajpcell.00551.2024

Denise Lucas, Tamal Sarkar, Clara Y Niemeyer, Julian C Harnoss, Martin Schneider, Moritz J Strowitzki, Jonathan M Harnoss

引用次数: 0

Abstract

[Figure: see text].

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IRE1是胰腺癌的一个有希望的治疗靶点。

胰腺癌（PC）是最具侵袭性的恶性肿瘤之一，其特点是发病率上升，预后不良。尽管最近取得了进展，手术切除联合化疗仍然是唯一可能治愈的治疗选择。因此，寻找新的治疗靶点和制定有效的治疗策略至关重要。胰腺导管腺癌（PDAC）是PC最常见的形式，起源于外分泌细胞，并受到内在和外在的细胞应激，包括癌基因激活、肿瘤抑制因子丧失、缺氧和免疫抑制的肿瘤微环境（TME）和化疗，导致内质网（ER）内错误折叠蛋白的积累。内质网蛋白平衡的丧失激活未折叠蛋白反应（UPR），这是一种细胞内传感信号网络，使癌细胞能够减轻内质网应激并恢复细胞蛋白平衡。UPR关键传感器insitol - requiring Enzyme 1 （IRE1）是一种内质膜蛋白，通过胞质激酶- rna酶模块激活转录因子X-Box protein 1 Spliced (XBP1s)，促进蛋白质折叠、分泌能力和错误折叠蛋白的蛋白酶体降解。此外，它通过支架相互作用调节各种mRNA的ire1依赖性衰变（RIDD）和功能。在这篇综述中，我们综合了目前关于IRE1在PDAC肿瘤发生、进展、转移和耐药中的细胞自主和细胞非自主作用的证据，并概述了研究IRE1作为潜在治疗靶点的重点研究方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American journal of physiology. Cell physiology 生物-生理学

CiteScore

9.10

自引率

1.80%

发文量

252

审稿时长

1 months

期刊介绍： The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.