SHP1 Decreases Level of P-STAT3 (Ser727) and Inhibits Proliferation and Migration of Pancreatic Cancer Cells.

IF 2.1 4区医学 Q3 TOXICOLOGY

Journal of Environmental Pathology Toxicology and Oncology Pub Date : 2021-01-01 DOI:10.1615/JEnvironPatholToxicolOncol.2020035980

Mingming Zhang, Xiaoru Hu, Ye Kang, Zhe Wang, Wenyang Zhou, Chang Liu, Xianghong Yang

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引用次数: 1

Abstract

Purpose: To identify the direct effects and functional mechanisms of SHP1, plus its relationship with STAT3 in pancreatic cancer.

Methods: Immunohistochemistry and Western blot assays were used to test SHP1 expression in pancreatic cancer. The functions of SHP1 in pancreatic cancer cells were analyzed by cell viability, colony formation, flow cytometric analysis of apoptosis, migration and invasion assays. Co-immunoprecipitation, combined with shotgun mass spectrometry, verified the direct or indirect interactions with JAK1 and p-STAT3(Ser727). Non-labeling and quantitative proteomics analysis evaluated the effect of SHP1 on protein expression levels. PRM phosphorylation modification of quantitative proteomics analysis confirmed p-STAT3(Ser727) levels.

Results: SHP1 was missing or weakly expressed in human pancreatic ductal adenocarcinoma tissues and cells: PANC-1, AsPC-1, BxPC-3, and SW1990. SHP1 inhibited cell proliferation and migration. SHP1 had a slight effect on the protein expression level of PANC-1 cells. The level of p-STAT3(Ser727) was decreased by SHP1 at 0.53 multiple. Co-IP analysis revealed no direct or indirect interactions between SHP1and p-STAT3(Ser727) in protein complex patterns.

Conclusion: These results suggest that SHP1 negatively regulate pancreatic cancer cells progression. It inhibits STAT3 activation by decreasing STAT3 phosphorylation at serine 727.

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SHP1 降低 P-STAT3 (Ser727) 的水平并抑制胰腺癌细胞的增殖和迁移

目的：明确SHP1在胰腺癌中的直接作用和功能机制，以及它与STAT3的关系：方法：采用免疫组化和 Western 印迹检测 SHP1 在胰腺癌中的表达。通过细胞活力、集落形成、流式细胞仪分析凋亡、迁移和侵袭实验分析了 SHP1 在胰腺癌细胞中的功能。共免疫沉淀结合枪式质谱法验证了SHP1与JAK1和p-STAT3(Ser727)的直接或间接相互作用。非标记和定量蛋白质组学分析评估了 SHP1 对蛋白质表达水平的影响。定量蛋白质组学分析的PRM磷酸化修饰证实了p-STAT3(Ser727)的水平：结果：SHP1在人胰腺导管腺癌组织和细胞中缺失或弱表达：结果：SHP1在人胰腺导管腺癌组织和细胞（PANC-1、AsPC-1、BxPC-3和SW1990）中缺失或弱表达。SHP1 可抑制细胞增殖和迁移。SHP1 对 PANC-1 细胞的蛋白表达水平有轻微影响。SHP1使p-STAT3(Ser727)的水平下降了0.53倍。Co-IP分析表明，SHP1与p-STAT3(Ser727)在蛋白复合物模式中没有直接或间接的相互作用：这些结果表明，SHP1 对胰腺癌细胞的进展具有负调控作用。结论：这些结果表明，SHP1 对胰腺癌细胞的进展有负向调节作用，它通过降低 STAT3 在丝氨酸 727 处的磷酸化来抑制 STAT3 的活化。

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

Journal of Environmental Pathology Toxicology and Oncology 医学-毒理学

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Environmental Pathology, Toxicology and Oncology publishes original research and reviews of factors and conditions that affect human and animal carcinogensis. Scientists in various fields of biological research, such as toxicologists, chemists, immunologists, pharmacologists, oncologists, pneumologists, and industrial technologists, will find this journal useful in their research on the interface between the environment, humans, and animals.