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鞘氨醇激酶1通过激活淋巴管内皮细胞中的细胞外信号调节激酶促进胰腺癌淋巴管生成。

SPHK1 Promotes Pancreatic Cancer Lymphangiogenesis Through the Activation of ERK in LECs.

作者信息

Yu Mengsi, Wang Song, Zeng Yujie, Liu Pingli, Li Hui

机构信息

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830054, China.

Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

出版信息

Mol Biotechnol. 2025 Jun;67(6):2246-2253. doi: 10.1007/s12033-024-01192-9. Epub 2024 Jun 11.

DOI:10.1007/s12033-024-01192-9
PMID:38861202
Abstract

Lymphatic metastasis is related to an unsatisfactory prognosis in pancreatic cancer. Sphingosine kinase 1 (SPHK1) is an oncogene in cancer. However, the potential effect of SPHK1 on the lymphangiogenesis of pancreatic cancer is little known. In this study, the expression level and role of SPHK1 in pancreatic cancer were evaluated to explore the underlying mechanism involved. The expression of SPHK1 and the lymphatic vessel density (LVD) in pancreatic cancer patient tissue were investigated by immunohistochemistry. The role of SPHK1 in lymphangiogenesis was verified in vitro. Elevated expression of SPHK1 was strongly related to high LVD in pancreatic cancer patient tissue. Silencing of SPHK1 in pancreatic cancer cells observably inhibited lymphangiogenesis. Furthermore, the downregulation of SPHK1 markedly attenuated the phosphorylation of extracellular signal-regulated kinase in lymphatic endothelial cells. This study revealed that SPHK1 might play a crucial role in pancreatic cancer lymphangiogenesis.

摘要

淋巴转移与胰腺癌预后不佳相关。鞘氨醇激酶1(SPHK1)是癌症中的一种癌基因。然而,SPHK1对胰腺癌淋巴管生成的潜在影响鲜为人知。在本研究中,评估了SPHK1在胰腺癌中的表达水平和作用,以探索其中潜在的机制。通过免疫组织化学研究了胰腺癌患者组织中SPHK1的表达和淋巴管密度(LVD)。在体外验证了SPHK1在淋巴管生成中的作用。胰腺癌患者组织中SPHK1的高表达与高LVD密切相关。沉默胰腺癌细胞中的SPHK1可明显抑制淋巴管生成。此外,SPHK1的下调显著减弱了淋巴管内皮细胞中细胞外信号调节激酶的磷酸化。本研究表明,SPHK1可能在胰腺癌淋巴管生成中起关键作用。

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本文引用的文献

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Metabolites. 2023 Nov 4;13(11):1132. doi: 10.3390/metabo13111132.
2
M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma.M2 巨噬细胞分泌的外泌体促进肝癌转移并增加血管通透性。
Cell Commun Signal. 2023 Oct 30;21(1):299. doi: 10.1186/s12964-022-00872-w.
3
Clinical Significance of Phosphorylated Sphingosine Kinase 1 Expression in Pancreatic Ductal Adenocarcinoma.
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Anticancer Res. 2023 Sep;43(9):3969-3977. doi: 10.21873/anticanres.16584.
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S100A4-dependent glycolysis promotes lymphatic vessel sprouting in tumor.S100A4 依赖性糖酵解促进肿瘤淋巴管生成。
Angiogenesis. 2023 Feb;26(1):19-36. doi: 10.1007/s10456-022-09845-6. Epub 2022 Jul 12.
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Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression.淋巴管生成需要 Ang2/Tie/PI3K 信号通路来促进 VEGFR3 的细胞表面表达。
J Clin Invest. 2022 Aug 1;132(15). doi: 10.1172/JCI155478.
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J Clin Invest. 2022 Jul 15;132(14). doi: 10.1172/JCI157644.
7
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