TY - JOUR
T1 - Autocrine STIP1 signaling promotes tumor growth and is associated with disease outcome in hepatocellular carcinoma
AU - Chen, Zebin
AU - Xu, Lixia
AU - Su, Tianhong
AU - Ke, Zunfu
AU - Peng, Zhenwei
AU - Zhang, Ning
AU - Peng, Sui
AU - Zhang, Qiuyang
AU - Liu, Gengxun
AU - Wei, Guangyan
AU - Guo, Yu
AU - He, Minghui
AU - Kuang, Ming
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China ( 81301842/81401999/81502078 ), the State Key Program of National Natural Science Foundation of Guangdong, China ( 2015A030311039 ), and the Science and Technology Planning Project of Guangdong Province, China ( 2014A020212390 ). Authors declare no conflict of interest.
Publisher Copyright:
© 2017
PY - 2017/11/4
Y1 - 2017/11/4
N2 - Stress-induced phosphoprotein 1 (STIP1) is an adaptor protein that bridges between HSP70 and HSP90 folding and a secretory protein which regulates malignant cell growth. However, the role of STIP1 in hepatocellular carcinoma (HCC) remains unknown. Here, we found high expression of STIP1 in tumors was associated with worse overall survival (41.3 vs 62.7 months, P < 0.001) in 231 HCC patients. STIP1 was overexpressed in HCC tissues compared to adjacent non-tumor liver tissue (64.9% vs 4.0% P < 0.001), and serum STIP1 levels of HCC patients were elevated compared to healthy controls (P < 0.001). Mechanistically, STIP1 promoted HCC growth through PI3K-AKT-dependent anti-apoptotic pathway. STIP1 mediated cell growth in an autocrine fashion, which could be suppressed either by neutralizing extracellular STIP1 or by knocking down intracellular STIP1. In xenograft mouse model, knockdown of STIP1 significantly reduced tumor growth (P < 0.001). In conclusion, STIP1 is upregulated in HCC and associated with poor clinical prognosis. Blocking STIP1 activity suppresses HCC cell growth, providing the rationale for STIP1 as a potential therapeutic target in HCC.
AB - Stress-induced phosphoprotein 1 (STIP1) is an adaptor protein that bridges between HSP70 and HSP90 folding and a secretory protein which regulates malignant cell growth. However, the role of STIP1 in hepatocellular carcinoma (HCC) remains unknown. Here, we found high expression of STIP1 in tumors was associated with worse overall survival (41.3 vs 62.7 months, P < 0.001) in 231 HCC patients. STIP1 was overexpressed in HCC tissues compared to adjacent non-tumor liver tissue (64.9% vs 4.0% P < 0.001), and serum STIP1 levels of HCC patients were elevated compared to healthy controls (P < 0.001). Mechanistically, STIP1 promoted HCC growth through PI3K-AKT-dependent anti-apoptotic pathway. STIP1 mediated cell growth in an autocrine fashion, which could be suppressed either by neutralizing extracellular STIP1 or by knocking down intracellular STIP1. In xenograft mouse model, knockdown of STIP1 significantly reduced tumor growth (P < 0.001). In conclusion, STIP1 is upregulated in HCC and associated with poor clinical prognosis. Blocking STIP1 activity suppresses HCC cell growth, providing the rationale for STIP1 as a potential therapeutic target in HCC.
KW - Apoptosis
KW - Hepatocellular carcinoma
KW - Prognosis
KW - Secretory protein
KW - Stress-induced phosphoprotein 1
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U2 - 10.1016/j.bbrc.2017.09.016
DO - 10.1016/j.bbrc.2017.09.016
M3 - Article
C2 - 28887036
AN - SCOPUS:85028917869
SN - 0006-291X
VL - 493
SP - 365
EP - 372
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -