TY - JOUR
T1 - The HBx–CTTN interaction promotes cell proliferation and migration of hepatocellular carcinoma via CREB1
AU - Li, Yajun
AU - Fu, Yongming
AU - Hu, Xingwang
AU - Sun, Lunquan
AU - Tang, Daolin
AU - Li, Ning
AU - Peng, Fang
AU - Fan, Xue gong
N1 - Funding Information:
This work was supported by a grant from International Scientific and Technology Cooperation Program of China (No. 2015DFA31490), grants from National Natural Science Foundation of China (No. 81602572, 81873574, and 81402623), and the Natural Science Foundation of Hunan Province (2017JJ3496 and 2018ZX10732202).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Hepatitis B virus-encoded X protein (HBx) acts as a tumor promoter during hepatocellular carcinoma (HCC) development, probably by regulating the expression of host proteins through protein–protein interaction. A proteomics approach was used to identify HBx-interacting proteins involved in HBx-induced hepatocarcinogenesis. We validated the proteomics findings by co-immunoprecipitation and confocal microscopy. We performed cell proliferation, migration assays and cell cycle analyses in HCC cells. Finally, we confirmed the clinical significance of our findings in samples from patients. We found that cortactin (CTTN) is a novel HBx-interacting protein, and HBx regulates the expression of CTTN in the HCC cell lines MHCC-LM3 and HepG2. Mechanistically, by upregulating the expression of cAMP response element-binding protein (CREB1) and its downstream targets, such as cyclin D1 and MMP-9, the effects of the HBx-CTTN interaction on the enhancement of cellular proliferation and migration were maintained by inhibiting cell cycle arrest. In addition, we demonstrated that the levels of CTTN and CREB1 were closely correlated in clinical samples from HBV-infected patients with HCC. Overall, our data suggests that HBx contributes to cell migration and proliferation of HCC cells by interacting with CTTN and regulating the expression of CTTN and CREB1. Therefore, the HBx/CTTN/CREB1 axis is a potential novel therapeutic target in HCC.
AB - Hepatitis B virus-encoded X protein (HBx) acts as a tumor promoter during hepatocellular carcinoma (HCC) development, probably by regulating the expression of host proteins through protein–protein interaction. A proteomics approach was used to identify HBx-interacting proteins involved in HBx-induced hepatocarcinogenesis. We validated the proteomics findings by co-immunoprecipitation and confocal microscopy. We performed cell proliferation, migration assays and cell cycle analyses in HCC cells. Finally, we confirmed the clinical significance of our findings in samples from patients. We found that cortactin (CTTN) is a novel HBx-interacting protein, and HBx regulates the expression of CTTN in the HCC cell lines MHCC-LM3 and HepG2. Mechanistically, by upregulating the expression of cAMP response element-binding protein (CREB1) and its downstream targets, such as cyclin D1 and MMP-9, the effects of the HBx-CTTN interaction on the enhancement of cellular proliferation and migration were maintained by inhibiting cell cycle arrest. In addition, we demonstrated that the levels of CTTN and CREB1 were closely correlated in clinical samples from HBV-infected patients with HCC. Overall, our data suggests that HBx contributes to cell migration and proliferation of HCC cells by interacting with CTTN and regulating the expression of CTTN and CREB1. Therefore, the HBx/CTTN/CREB1 axis is a potential novel therapeutic target in HCC.
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U2 - 10.1038/s41419-019-1650-x
DO - 10.1038/s41419-019-1650-x
M3 - Article
C2 - 31138777
AN - SCOPUS:85066304579
SN - 2041-4889
VL - 10
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 6
M1 - 405
ER -