Journal of Hepatocellular Carcinoma (Jul 2021)

SERPINA11 Inhibits Metastasis in Hepatocellular Carcinoma by Suppressing MEK/ERK Signaling Pathway

  • Song Y,
  • Li Z,
  • Li L,
  • Zhou H,
  • Zeng TT,
  • Jin C,
  • Lin JR,
  • Gao S,
  • Li Y,
  • Guan XY,
  • Zhu YH

Journal volume & issue
Vol. Volume 8
pp. 759 – 771

Abstract

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Ye Song,1,2,* Zhuo Li,1,* Lei Li,3,* Houming Zhou,4 Ting-Ting Zeng,1 Chuan Jin,2 Jin-Rong Lin,2 Sha Gao,2 Yan Li,1 Xin-Yuan Guan,1,3 Ying-Hui Zhu1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China; 2Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510000, People’s Republic of China; 3Department of Clinical Oncology, The University of Hong Kong, Hong Kong, People’s Republic of China; 4Department of Chinese Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying-Hui ZhuState Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, People’s Republic of ChinaTel + 86-20-87342283Email [email protected] GuanDepartment of Clinical Oncology, The University of Hong Kong, Room L10-56, 10/F, Laboratory Block, 21 Sassoon Road, Hong Kong, People’s Republic of ChinaTel +86 852-39179782Fax + 852-28169126Email [email protected]: By using integrative RNA sequencing analysis, we identified a novel tumor suppressor, serpin family A member 11 (SERPINA11), which is a serine proteinase inhibitor that belongs to the serpin superfamily. However, the function of SERPINA11 in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the role and molecular mechanism of SERPINA11 in HCC.Methods: Gene expression patterns of SERPINA11 were analyzed in tissue samples of HCC patients by qRT-PCR. In vitro and in vivo experiments were performed to characterize the function and molecular mechanism of SERPINA11 in the tumor metastasis capacity.Results: SERPINA11 was downregulated in approximately 50% of HCC and significantly associated with metastasis and poor outcome of patients. Functional study demonstrated that SERPINA11 could inhibit cell growth, cell migration and tumor metastasis. Mechanistic investigations suggested that SERPINA11 accelerated urokinase-type plasminogen activator (uPA) degradation to suppress extracellular signal-regulated kinase (ERK1/2) phosphorylation, and thereby subdued metastatic capabilities of HCC cells.Conclusion: SERPINA11 plays an important tumor suppressive role in HCC, with possible use as a biomarker and an intervention point for new therapeutic strategies.Keywords: SERPINA11, HCC, metastasis, uPA, ERK

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