HSP70 promotes pancreatic cancer cell epithelial-mesenchymal transformation and growth via the NF-κB signaling pathway.

IF 1.7 4区 医学 Q3 GASTROENTEROLOGY & HEPATOLOGY Pancreas Pub Date : 2024-08-16 DOI:10.1097/MPA.0000000000002398
Liumei Xiong, Danming Li, Gui Xiao, Sipin Tan, Linfang Xu, Guiliang Wang
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Abstract

Objective: To study the effects of HSP70 on proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) of pancreatic cancer cells and explore its underlying mechanisms.

Methods: Pancreatic cancer cell models with either reduced HSP70 or increased HSP70 expression were established. RT-qPCR and Western blot assays were used to determine mRNA and protein levels of HSP70, IKK/IκBa/NF-κB signaling pathway-related genes, and EMT markers. The CCK-8 and cell cloning assays were used to evaluate cell proliferation and cloning abilities. Transwell and wound healing assays were used to assess the invasive and migratory properties of the cells. Effects of NF-κB signaling modulation were explored using an IKK inhibitor (BAY11-7082) and an IKK overexpression vector (pCMV-IKK). Electrophoretic mobility shift assay (EMSA) and luciferase reporter assays were conducted to analyze NF-κB's promoter binding and transcriptional activities.

Results: HSP70 knockdown inhibited p-p65 nuclear translocation and reduced the expression of p-p65, p-IKKα/β, p-IκBα, N-cadherin, Vimentin, and Twist. It also decreased NF-κB's promoter binding and transcriptional activities, increased E-cadherin levels, and suppressed pancreatic cancer cell proliferation, cloning, migration, and invasion. In contrast, HSP70 overexpression led to increased expression of p-p65, p-IKKα/β, p-IκBα, N-cadherin, Vimentin, and Twist, decreased E-cadherin levels, and enhanced cell proliferation, cloning, migration, and invasion capabilities. NF-κB signaling pathway modulation reversed EMT changes induced by altered HSP70 expression levels. rhHSP70 also increased p-IKKα/β and p-IκBα protein levels.

Conclusion: HSP70 promotes the EMT and enhances pancreatic cancer cell proliferation, migration, and invasion by activating the NF-κB pathway.

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HSP70 通过 NF-κB 信号通路促进胰腺癌细胞上皮-间质转化和生长。
目的研究 HSP70 对胰腺癌细胞增殖、迁移、侵袭和上皮-间质转化(EMT)的影响,并探索其潜在机制:方法:建立 HSP70 表达减少或增加的胰腺癌细胞模型。采用 RT-qPCR 和 Western 印迹分析法测定 HSP70、IKK/IκBa/NF-κB 信号通路相关基因和 EMT 标志物的 mRNA 和蛋白水平。CCK-8 和细胞克隆试验用于评估细胞增殖和克隆能力。透孔试验和伤口愈合试验用于评估细胞的侵袭和迁移特性。使用 IKK 抑制剂(BAY11-7082)和 IKK 过表达载体(pCMV-IKK)探讨了 NF-κB 信号调节的效果。电泳迁移实验(EMSA)和荧光素酶报告实验分析了NF-κB的启动子结合和转录活性:结果:HSP70敲除抑制了p-p65的核转位,并降低了p-p65、p-IKKα/β、p-IκBα、N-cadherin、Vimentin和Twist的表达。它还能降低 NF-κB 的启动子结合和转录活性,提高 E-cadherin 水平,抑制胰腺癌细胞的增殖、克隆、迁移和侵袭。相反,过量表达 HSP70 会导致 p-p65、p-IKKα/β、p-IκBα、N-cadherin、Vimentin 和 Twist 表达增加,E-cadherin 水平降低,细胞增殖、克隆、迁移和侵袭能力增强。NF-κB信号通路调控逆转了HSP70表达水平改变所诱导的EMT变化,rhHSP70还增加了p-IKKα/β和p-IκBα蛋白水平:结论:HSP70 通过激活 NF-κB 通路促进 EMT 并增强胰腺癌细胞的增殖、迁移和侵袭。
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
Pancreas
Pancreas 医学-胃肠肝病学
CiteScore
4.70
自引率
3.40%
发文量
289
审稿时长
1 months
期刊介绍: Pancreas provides a central forum for communication of original works involving both basic and clinical research on the exocrine and endocrine pancreas and their interrelationships and consequences in disease states. This multidisciplinary, international journal covers the whole spectrum of basic sciences, etiology, prevention, pathophysiology, diagnosis, and surgical and medical management of pancreatic diseases, including cancer.
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