Tumor Biology

, Volume 35, Issue 8, pp 7999–8005 | Cite as

CKAP4 inhibited growth and metastasis of hepatocellular carcinoma through regulating EGFR signaling

  • Shuang-xi Li
  • Li-juan Liu
  • Li-wei Dong
  • Hong-guang Shi
  • Yu-fei Pan
  • Ye-xiong Tan
  • Jian Zhang
  • Bo Zhang
  • Zhi-wen Ding
  • Tian-yi Jiang
  • He-ping Hu
  • Hong-yang Wang
Research Article

Abstract

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.

Keywords

Cytoskeleton-associated membrane protein 4 Hepatocellular carcinoma EGFR Metastasis 

Abbreviations

APF

Anti-proliferative factor

CKAP4

Cytoskeleton-associated membrane protein 4

EGFR

Epithelial growth factor receptor

EMT

Epithelial-mesenchymal transition

HCC

Hepatocellular carcinoma

TACE

Transcatheter arterial chemoembolization

Notes

Acknowledgments

Research was supported by grants from National Natural Science Foundation of China (81000971, 81370066), the Funds for Creative Research Groups of China (81221061), the State Key Project for Liver Cancer (2012ZX10002-009, 2013ZX10002-010), and the medical science and technology foundation of PLA for young scholars (I3QNP035).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Shuang-xi Li
    • 1
    • 4
  • Li-juan Liu
    • 1
    • 3
  • Li-wei Dong
    • 1
    • 3
  • Hong-guang Shi
    • 2
  • Yu-fei Pan
    • 1
    • 3
  • Ye-xiong Tan
    • 1
    • 3
  • Jian Zhang
    • 1
    • 3
  • Bo Zhang
    • 1
  • Zhi-wen Ding
    • 1
    • 3
  • Tian-yi Jiang
    • 1
    • 3
  • He-ping Hu
    • 4
  • Hong-yang Wang
    • 1
    • 3
    • 5
  1. 1.International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery InstituteThe Second Military Medical UniversityShanghaiPeople’s Republic of China
  2. 2.Division of Nephrology, Kidney Institute of PLA, Changzheng HospitalThe Second Military Medical UniversityShanghaiPeople’s Republic of China
  3. 3.National Institute for Liver Cancer ResearchShanghaiPeople’s Republic of China
  4. 4.Department of Liver Medicine, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China
  5. 5.State Key Laboratory of Oncogenes and related Genes, Shanghai Cancer Institute, Renji HospitalShanghai Jiaotong University School of MedicineShanghaiPeople’s Republic of China

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