ROCK1 通过 c-MYC/PFKFB3 通路调节胰腺癌中的糖酵解。

IF 2.8 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
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引用次数: 0

摘要

背景:Rho相关含线圈蛋白激酶(ROCKs)的失调与各种恶性肿瘤的转移和进展有关。然而,人们对异构体之一的 ROCK1 如何调节肿瘤细胞中的糖酵解尚不完全清楚。在此,我们试图阐明 ROCK1 如何通过调节糖酵解活性来影响胰腺癌(PC)的进展:方法:通过建立沉默细胞模型,在体外分析了 ROCK1 的生物学功能。免疫共沉淀证实了 ROCK1 与 c-MYC 之间的直接结合,荧光素酶报告实验显示了 c-MYC 与 PFKFB3 基因启动子的结合。这些结果在动物实验中得到了验证:结果:ROCK1在PC组织中高表达并富集于细胞质中,其高表达与预后不良有关。沉默 ROCK1 可抑制 PC 细胞的增殖和迁移,促进其凋亡。从机制上讲,ROCK1直接与c-MYC相互作用,促进其磷酸化(Ser 62)并抑制其降解,从而增加关键糖酵解调节因子PFKFB3的转录,增强糖酵解活性并促进PC生长。沉默ROCK1可提高体内和体外吉西他滨(GEM)的敏感性:结论:ROCK1能促进PC细胞的糖酵解活性,并通过c-MYC/PFKFB3信号通路促进PC肿瘤的生长。结论:ROCK1促进PC细胞的糖酵解活性,并通过c-MYC/PFKFB3信号通路促进PC肿瘤的生长。敲除ROCK1可抑制PC肿瘤在体内的生长,并提高PC肿瘤对吉西莫(GEM)的敏感性,从而为PC的临床治疗提供重要策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ROCK1 regulates glycolysis in pancreatic cancer via the c-MYC/PFKFB3 pathway

Background

Dysregulation of Rho-associated coiled coil-containing protein kinases (ROCKs) is involved in the metastasis and progression of various malignant tumors. However, how one of the isomers, ROCK1, regulates glycolysis in tumor cells is incompletely understood. Here, we attempted to elucidate how ROCK1 influences pancreatic cancer (PC) progression by regulating glycolytic activity.

Methods

The biological function of ROCK1 was analyzed in vitro by establishing a silenced cell model. Coimmunoprecipitation confirmed the direct binding between ROCK1 and c-MYC, and a luciferase reporter assay revealed the binding of c-MYC to the promoter of the PFKFB3 gene. These results were verified in animal experiments.

Results

ROCK1 was highly expressed in PC tissues and enriched in the cytoplasm, and its high expression was associated with a poor prognosis. Silencing ROCK1 inhibited the proliferation and migration of PC cells and promoted their apoptosis. Mechanistically, ROCK1 directly interacted with c-MYC, promoted its phosphorylation (Ser 62) and suppressed its degradation, thereby increasing the transcription of the key glycolysis regulatory factor PFKFB3, enhancing glycolytic activity and promoting PC growth. Silencing ROCK1 increased gemcitabine (GEM) sensitivity in vivo and in vitro.

Conclusions

ROCK1 promotes glycolytic activity in PC cells and promotes PC tumor growth through the c-MYC/PFKFB3 signaling pathway. ROCK1 knockdown can inhibit PC tumor growth in vivo and increase the GEM sensitivity of PC tumors, providing a crucial clinical therapeutic strategy for PC.

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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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