Molecules and Cells

  • 제45권12호
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  • Pages.935-949
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  • 2022
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Overexpression of KiSS1 Induces the Proliferation of Hepatocarcinoma and Increases Metastatic Potential by Increasing Migratory Ability and Angiogenic Capacity

  • Cho-Won, Kim (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Hong, Kyu, Lee (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Min-Woo, Nam (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Youngdong, Choi (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Kyung-Chul, Choi (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
  • 투고 : 2022.06.28
  • 심사 : 2022.09.30
  • 발행 : 2022.12.31
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초록

Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of β-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)- related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.

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과제정보

This work was supported by the Basic Science Research Program (2020R1A2C2006060) and the Global Research and Development Center (GRDC) Program (2017K1A4A3014959) through the National Research Foundation (NRF) of Korea, funded by the Ministry of Science and ICT. This work was also supported by the Sejong Fellowship of National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2021R1C1C2093998).

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