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

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

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Article number94
JournalCell Death Discovery
Issue number1
Publication statusPublished - 2021 Jun

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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