RETRACTED ARTICLE: KRAS activation in gastric cancer stem-like cells promotes tumor angiogenesis and metastasis
Abstract Our previous work showed that KRAS activation in gastric cancer cells leads to activation of an epithelial-to-mesenchymal transition (EMT) program and generation of cancer stem-like cells (CSCs). Here we analyze how this KRAS activation in gastric CSCs promotes tumor angiogenesis and metastasis. Gastric cancer CSCs were found to secrete pro-angiogenic factors such as vascular endothelial growth factor A (VEGF-A), and inhibition of KRAS markedly reduced secretion of these factors. In a genetically engineered mouse model, gastric tumorigenesis was markedly attenuated when both KRAS and VEGF-A signaling were blocked. In orthotropic implant and experimental metastasis models, silencing of KRAS and VEGF-A using shRNA in gastric CSCs abrogated primary tumor formation, lymph node metastasis, and lung metastasis far greater than individual silencing of KRAS or VEGF-A. Analysis of gastric cancer patient samples using RNA sequencing revealed a clear association between high expression of the gastric CSC marker CD44 and expression of both KRAS and VEGF-A, and high CD44 and VEGF-A expression predicted worse overall survival. In conclusion, KRAS activation in gastric CSCs enhances secretion of pro-angiogenic factors and promotes tumor progression and metastasis..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
BMC cancer - 23(2023), 1 vom: 22. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yoon, Changhwan [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| BKL: | |
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| Themen: |
Cancer stem cells |
| Anmerkungen: |
© The Author(s) 2023 |
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| doi: |
10.1186/s12885-023-11170-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract Our previous work showed that KRAS activation in gastric cancer cells leads to activation of an epithelial-to-mesenchymal transition (EMT) program and generation of cancer stem-like cells (CSCs). Here we analyze how this KRAS activation in gastric CSCs promotes tumor angiogenesis and metastasis. Gastric cancer CSCs were found to secrete pro-angiogenic factors such as vascular endothelial growth factor A (VEGF-A), and inhibition of KRAS markedly reduced secretion of these factors. In a genetically engineered mouse model, gastric tumorigenesis was markedly attenuated when both KRAS and VEGF-A signaling were blocked. In orthotropic implant and experimental metastasis models, silencing of KRAS and VEGF-A using shRNA in gastric CSCs abrogated primary tumor formation, lymph node metastasis, and lung metastasis far greater than individual silencing of KRAS or VEGF-A. Analysis of gastric cancer patient samples using RNA sequencing revealed a clear association between high expression of the gastric CSC marker CD44 and expression of both KRAS and VEGF-A, and high CD44 and VEGF-A expression predicted worse overall survival. In conclusion, KRAS activation in gastric CSCs enhances secretion of pro-angiogenic factors and promotes tumor progression and metastasis. | ||
| 650 | 4 | |a Gastric adenocarcinoma |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a KRAS |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Epithelial-to-mesenchymal transition |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Lu, Jun |4 aut | |
| 700 | 1 | |a Jun, Yukyung |4 aut | |
| 700 | 1 | |a Suh, Yun-Suhk |4 aut | |
| 700 | 1 | |a Kim, Bang-Jin |4 aut | |
| 700 | 1 | |a Till, Jacob E. |4 aut | |
| 700 | 1 | |a Kim, Jong Hyun |4 aut | |
| 700 | 1 | |a Keshavjee, Sara H. |4 aut | |
| 700 | 1 | |a Ryeom, Sandra |4 aut | |
| 700 | 1 | |a Yoon, Sam S. |4 aut | |
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