DYRK2 regulates epithelial-mesenchymal transition restriction in pancreatic cancer liver metastasis by inhibiting Twist.

IF 3 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Digestion Pub Date : 2024-11-19 DOI:10.1159/000541039

Hang Pan, Yin Liu, Kejiu Bao, Yulin Wang, Yuping Zhang, Lina Zhou

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引用次数: 0

Abstract

Objectives: To explore the underlying variables and molecular pathways leading to pancreatic cancer liver metastasis.

Methods: Hs766T and Hs766T-L3 cells were used to create in vitro and in vivo pancreatic cancer liver metastasis models. DYRK2 involvement in pancreatic cancer metastasis was investigated using cell adhesion assays, wound healing assays, and migration and invasion assays. To examine the link between DYRK2 expression and epithelial-mesenchymal transition, Western blot, quantitative real-time PCR, immunofluorescence assays, and immunoprecipitation (IP) were utilized. We found that mice with DYRK2 overexpression had a lower incidence of liver metastasis compared to controls.

Results: DYRK2 expression decreased pancreatic cancer tumorigenic activities, including proliferation, migration, and invasion. By analyzing the expression levels of epithelial-mesenchymal transition markers and IP results after overexpressing DYRK2, we found that DYRK2 decreased Twist levels by increasing Twist ubiquitination, thereby inhibiting epithelial-mesenchymal transition.

Conclusions: Our findings provide theoretical and experimental support for the ongoing development of DYRK2-based targeted therapies for pancreatic cancer liver metastases.

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DYRK2通过抑制Twist调节胰腺癌肝转移中的上皮-间质转化限制。

目的：探讨导致胰腺癌肝转移的潜在变量和分子通路：方法：使用 Hs766T 和 Hs766T-L3 细胞创建体外和体内胰腺癌肝转移模型。方法：用 Hs766T 和 Hs766T-L3 细胞创建体外和体内胰腺癌肝转移模型，使用细胞粘附试验、伤口愈合试验以及迁移和侵袭试验研究 DYRK2 参与胰腺癌转移的情况。为了研究 DYRK2 表达与上皮-间质转化之间的联系，研究人员采用了 Western 印迹、定量实时 PCR、免疫荧光检测和免疫沉淀（IP）等方法。我们发现，与对照组相比，DYRK2过表达的小鼠肝转移发生率较低：结果：DYRK2的表达降低了胰腺癌的致瘤活性，包括增殖、迁移和侵袭。通过分析过表达DYRK2后上皮-间质转化标志物的表达水平和IP结果，我们发现DYRK2通过增加Twist泛素化降低了Twist水平，从而抑制了上皮-间质转化：我们的研究结果为目前开发基于 DYRK2 的胰腺癌肝转移靶向疗法提供了理论和实验支持。

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

Digestion 医学-胃肠肝病学

CiteScore

7.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Digestion'' concentrates on clinical research reports: in addition to editorials and reviews, the journal features sections on Stomach/Esophagus, Bowel, Neuro-Gastroenterology, Liver/Bile, Pancreas, Metabolism/Nutrition and Gastrointestinal Oncology. Papers cover physiology in humans, metabolic studies and clinical work on the etiology, diagnosis, and therapy of human diseases. It is thus especially cut out for gastroenterologists employed in hospitals and outpatient units. Moreover, the journal''s coverage of studies on the metabolism and effects of therapeutic drugs carries considerable value for clinicians and investigators beyond the immediate field of gastroenterology.