GALNT5 promotes migration and invasion of pancreatic ductal adenocarcinoma cells by activating Erk signaling pathway

IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yongjia Zheng , Yuxing Lu , Fang Yuan , Yun Kong , Yang Mao , Shengjun Wang
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引用次数: 0

Abstract

Aberrant glycosylation has been implicated in promoting the progression and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the contribution of different glycosylation-related genes in PDAC remains to be clarified. In this study, we performed a differential analysis of RNA-Seq data from TCGA and GTEx and found GALNT5 as the most significant upregulated glycosylation-related gene in PDAC. Using publicly available single-cell sequencing data, we further revealed that GALNT5 is predominantly expressed in malignant ductal epithelial cells of PDAC. Correlation analysis indicated that GALNT5 is the essential member of the GALNT family associated with poor prognosis of PDAC. Overexpression of GALNT5 in PANC-1 or MIAPaCa-2 cells with low endogenous GALNT5 enhances migration and invasion. Conversely, knockdown of GALNT5 in AsPC-1 cells with high endogenous GALNT5 inhibits migration and invasion. Mechanistically, we discovered that GALNT5 activates the Erk signaling pathway in PDAC. Our findings suggest GALNT5 is a potential therapeutic target for PDAC.

Abstract Image

GALNT5通过激活Erk信号通路促进胰腺导管腺癌细胞的迁移和侵袭。
异常糖基化与促进胰腺导管腺癌(PDAC)的进展和转移有关。然而,不同糖基化相关基因在PDAC中的作用尚不清楚。在本研究中,我们对TCGA和GTEx的RNA-Seq数据进行了差异分析,发现GALNT5是PDAC中最显著的糖基化相关基因上调。利用公开的单细胞测序数据,我们进一步发现GALNT5主要在PDAC的恶性导管上皮细胞中表达。相关性分析提示GALNT5是与PDAC预后不良相关的GALNT家族的重要成员。在内源性GALNT5水平较低的PANC-1或MIAPaCa-2细胞中,过表达GALNT5可增强迁移和侵袭。相反,在具有高内源性GALNT5的AsPC-1细胞中,敲低GALNT5可抑制迁移和侵袭。在机制上,我们发现GALNT5激活PDAC中的Erk信号通路。我们的研究结果表明GALNT5是PDAC的潜在治疗靶点。
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来源期刊
Biochimica et biophysica acta. General subjects
Biochimica et biophysica acta. General subjects 生物-生化与分子生物学
CiteScore
6.40
自引率
0.00%
发文量
139
审稿时长
30 days
期刊介绍: BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.
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