CKAP4 inhibited growth and metastasis of hepatocellular carcinoma through regulating EGFR signaling.
CKAP4, one kind of type II trans-membrane protein, plays an important role to maintain endoplasmic reticulum structure and inhibits the proliferation of bladder cancer cells by combining its ligand anti-proliferative factor (APF). However, the biological function of CKAP4 in the progression of liver cancer has not been clearly demonstrated. In the present study, we knocked down or overexpressed CKAP4 in hepatocellular carcinoma (HCC) cells and cell proliferation, invasion, and migration capacities were investigated by CCK-8 and transwell assays. In vivo tumor model in mice was used to evaluate the role of CKAP4 on growth and metastasis of HCC. The data documented that HCC cells with high CKAP4 levels were featured by low proliferation capability as well as low invasion potential. Interestingly, we found that CKAP4 suppressed the activation of epithelial growth factor receptor (EGFR) signaling, which may partly explain the role of CKAP4 in cell biological behavior of HCC. Further study revealed that CKAP4 could associate with EGFR at basal status and the complex was reduced upon EGF stimulation, leading to release EGFR into cytoplasm. Thus, we demonstrate the novel mechanism, for the first time, expression of CKAP4 regulates progression and metastasis of HCC and it may provide therapeutic values in this tumor.
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, 225 Changhai Road, 200438, Shanghai, People's Republic of China.
Shuang-Xi
SX
Li
Li-Juan
LJ
Liu
Li-Wei
LW
Dong
Hong-Guang
HG
Shi
Yu-Fei
YF
Pan
Ye-Xiong
YX
Tan
Jian
J
Zhang
Bo
B
Zhang
Zhi-Wen
ZW
Ding
Tian-Yi
TY
Jiang
He-Ping
HP
Hu
Hong-Yang
HY
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C081876:CKAP4 protein, human; C098587:GAB1 protein, human; D008565:Membrane Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors