| Autor: |
Changhwan Yoon, Jun Lu, Yukyung Jun, Yun-Suhk Suh, Bang-Jin Kim, Jacob E. Till, Jong Hyun Kim, Sara H. Keshavjee, Sandra Ryeom, Sam S. Yoon |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
BMC Cancer, Vol 23, Iss 1, Pp 1-16 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2407 |
| DOI: |
10.1186/s12885-023-11170-0 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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