Hepatoma-derived growth factor supports the antiapoptosis and profibrosis of pancreatic stellate cells

Yi Ting Chen, Feng Wei Chen, Tsung Hao Chang, Tso Wen Wang, Teng Po Hsu, Jhih Ying Chi, Yu Wei Hsiao, Chien Feng Li, Ju Ming Wang

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Pancreatic cancer is refractory and is characterized by extensively surrounding and intratumor fibrotic reactions that are contributed by activated pancreatic stellate cells (PSCs). Herein, we show that CCAAT/enhancer-binding protein δ (CEBPD) responds to transforming growth factor-β1 (TGF-β1) through reciprocal loop regulation and that activated hypoxia inducible factor-1α (HIF-1α) further contributes to the upregulation of the hepatoma-derived growth factor (HDGF) gene. Secreted HDGF contributes to the antiapoptosis of PSCs and consequently leads to the synthesis and deposition of extracellular matrix proteins for stabilizing PSC/pancreatic cancer cell (PCC) tumor foci. This result agrees with the observation that severe stromal growth positively correlated with stromal HDGF and CEBPD expression in pancreatic cancer specimens. Collectively, the identification of the TGF-β1-activated CEBPD/HIF-1α/HDGF axis provides new insights into novel discoveries of HDGF in the antiapoptosis and profibrosis of PSCs and the outgrowth of PCCs.

Original languageEnglish
Pages (from-to)180-190
Number of pages11
JournalCancer Letters
Publication statusPublished - 2019 Aug 10

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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