Abstract
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 language | English |
|---|---|
| Pages (from-to) | 180-190 |
| Number of pages | 11 |
| Journal | Cancer Letters |
| Volume | 457 |
| DOIs | |
| Publication status | Published - 2019 Aug 10 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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Hepatoma-derived growth factor supports the antiapoptosis and profibrosis of pancreatic stellate cells. / Chen, Yi Ting; Chen, Feng Wei; Chang, Tsung Hao; Wang, Tso Wen; Hsu, Teng Po; Chi, Jhih Ying; Hsiao, Yu Wei; Li, Chien Feng; Wang, Ju-Ming.
In: Cancer Letters, Vol. 457, 10.08.2019, p. 180-190.Research output: Contribution to journal › Article
TY - JOUR
T1 - Hepatoma-derived growth factor supports the antiapoptosis and profibrosis of pancreatic stellate cells
AU - Chen, Yi Ting
AU - Chen, Feng Wei
AU - Chang, Tsung Hao
AU - Wang, Tso Wen
AU - Hsu, Teng Po
AU - Chi, Jhih Ying
AU - Hsiao, Yu Wei
AU - Li, Chien Feng
AU - Wang, Ju-Ming
PY - 2019/8/10
Y1 - 2019/8/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85066061791&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066061791&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2019.05.001
DO - 10.1016/j.canlet.2019.05.001
M3 - Article
VL - 457
SP - 180
EP - 190
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
ER -