S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE/NF-kB/VEGF-D pathway
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
Patients diagnosed with lymph node (LN) metastatic liver cancer face an exceedingly grim prognosis. In-depth analysis of LN metastatic patients' characteristics and tumor cells' interactions with human lymphatic endothelial cells (HLECs), can provide important biological and therapeutic insights. Here we identify at the single-cell level that S100A6 expression differs between primary tumor and their LN metastasis. Of particular significance, we uncovered the disparity in S100A6 expression between tumors and normal tissues is greater in intrahepatic cholangiocarcinoma (ICC) patients, frequently accompanied by LN metastases, than that in hepatocellular carcinoma (HCC), with rare occurrence of LN metastasis. Furthermore, in the infrequent instances of LN metastasis in HCC, heightened S100A6 expression was observed, suggesting a critical role of S100A6 in the process of LN metastasis. Subsequent experiments further uncovered that S100A6 secreted from tumor cells promotes lymphangiogenesis by upregulating the expression and secretion of vascular endothelial growth factor-D (VEGF-D) in HLECs through the RAGE/NF-kB/VEGF-D pathway while overexpression of S100A6 in tumor cells also augmented their migration and invasion. Taken together, these data reveal the dual effects of S100A6 in promoting LN metastasis in liver cancer, thus highlighting its potential as a promising therapeutic target.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:587 |
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| Enthalten in: |
Cancer letters - 587(2024) vom: 10. März, Seite 216709 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, TianYi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.03.2024 Date Revised 26.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.canlet.2024.216709 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368406539 |
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| 520 | |a Patients diagnosed with lymph node (LN) metastatic liver cancer face an exceedingly grim prognosis. In-depth analysis of LN metastatic patients' characteristics and tumor cells' interactions with human lymphatic endothelial cells (HLECs), can provide important biological and therapeutic insights. Here we identify at the single-cell level that S100A6 expression differs between primary tumor and their LN metastasis. Of particular significance, we uncovered the disparity in S100A6 expression between tumors and normal tissues is greater in intrahepatic cholangiocarcinoma (ICC) patients, frequently accompanied by LN metastases, than that in hepatocellular carcinoma (HCC), with rare occurrence of LN metastasis. Furthermore, in the infrequent instances of LN metastasis in HCC, heightened S100A6 expression was observed, suggesting a critical role of S100A6 in the process of LN metastasis. Subsequent experiments further uncovered that S100A6 secreted from tumor cells promotes lymphangiogenesis by upregulating the expression and secretion of vascular endothelial growth factor-D (VEGF-D) in HLECs through the RAGE/NF-kB/VEGF-D pathway while overexpression of S100A6 in tumor cells also augmented their migration and invasion. Taken together, these data reveal the dual effects of S100A6 in promoting LN metastasis in liver cancer, thus highlighting its potential as a promising therapeutic target | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Liver cancer | |
| 650 | 4 | |a Lymph node metastasis | |
| 650 | 4 | |a Lymphangiogenesis | |
| 650 | 4 | |a S100A6 | |
| 650 | 7 | |a Vascular Endothelial Growth Factor D |2 NLM | |
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| 650 | 7 | |a S100 Calcium Binding Protein A6 |2 NLM | |
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| 700 | 1 | |a Ruan, YeLing |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, JingWei |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, YangTao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Hu |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, XiuJun |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, JunJie |e verfasserin |4 aut | |
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