Fibroblast CEBPD/SDF4 axis in response to chemotherapy-induced angiogenesis through CXCR4

Autor: Jhih-Ying Chi, Yu-Wei Hsiao, Hai-Ling Liu, Xin-Juan Fan, Xiang-Bo Wan, Tsung-Lin Liu, Sheng-Jou Hung, Yi-Ting Chen, Hsin-Yin Liang, Ju-Ming Wang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Death Discovery, Vol 7, Iss 1, Pp 1-16 (2021)
Druh dokumentu: article
ISSN: 2058-7716
DOI: 10.1038/s41420-021-00478-0
Popis: Abstract Cancer-associated fibroblasts (CAFs) play an essential role in supporting cancer progression. However, the details and consequent effects in response to the communication between CAFs and angiogenesis remain largely uninvestigated, especially in anticancer drug treatments. We found that cisplatin and 5-fluorouracil could induce fibroblast differentiation toward myofibroblasts via CCAAT/enhancer-binding protein delta (CEBPD) and consequently promote proliferation, migration, and in vitro tube formation of vascular endothelial cells and angiogenesis in vivo. Stromal-cell-derived factor 4 (SDF4) is responsive to anticancer drugs via CEBPD activation in CAFs and contributes to create a permissive environment for tumor cell angiogenesis and promotion of distant metastasis. Importantly, we demonstrated that SDF4 interacts with CXCR4 to trigger VEGFD expression through the activation of the ERK1/2 and p38 pathways in endothelial cells. Taken together, our novel findings support that SDF4 can be a therapeutic target in inhibition of angiogenesis for chemotherapy drug-administrated cancer patients.
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