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Cellular and Molecular Biology

IQGAP1 promotes anoikis resistance and metastasis through Rac1-dependent ROS accumulation and activation of Src/FAK signalling in hepatocellular carcinoma

British Journal of Cancer volume 123, pages 1154–1163 (2020)Cite this article

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A Correction to this article was published on 10 June 2021

A Correction to this article was published on 06 April 2021

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Abstract

Background

Hepatitis B virus (HBV) has a crucial role in the progression of hepatocellular carcinoma (HCC). Tumour cells must develop anoikis resistance in order to survive before metastasis. This study aimed to investigate the mechanism of IQGAP1 in HBV-mediated anoikis evasion and metastasis in HCC cells.

Methods

IQGAP1 expression was detected by immunohistochemistry, real-time PCR and immunoblot analysis. Lentiviral-mediated stable upregulation or knockdown of IGAQP1, immunoprecipitation, etc. were used in function and mechanism study.

Results

IQGAP1 was markedly upregulated in HBV-positive compared with HBV-negative HCC cells and tissues. IQGAP1 was positively correlated to poor prognosis of HBV-associated HCC patients. IQGAP1 overexpression significantly enhanced the anchorage-independent growth and metastasis, whereas IQGAP1-deficient HCC cells are more sensitive to anoikis. Mechanistically, we found that HBV-induced ROS enhanced the association of IQGAP1 and Rac1 that activated Rac1, leading to phosphorylation of Src/FAK pathway. Antioxidants efficiently inhibited IQGAP1-mediated anoikis resistance and metastasis.

Conclusions

Our study indicated an important mechanism by which upregulated IQGAP1 by HBV promoted anoikis resistance, migration and invasion of HCC cells through Rac1-dependent ROS accumulation and activation of Src/FAK signalling, suggesting IQGAP1 as a prognostic indicator and a novel therapeutic target in HCC patients with HBV infection.

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Fig. 1: IQGAP1 is upregulated in HBV-associated HCC cells and tissues.
Fig. 2: IQGAP1 promotes anoikis resistance, migration and invasion of HCC cells.
Fig. 3: ROS are required for IQGAP1-mediated anoikis resistance and metastasis in HCC cells.
Fig. 4: Rac1 acivation is essential for IQGAP1-mediated ROS production, anoikis resistance and metastasis in HCC cells.
Fig. 5: IQGAP1 activates Src/FAK signalling pathway.
Fig. 6: IQGAP1 enhances anoikis resistance and metastasis of HCC cells in vivo.

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Author information

Author notes

  1. These authors contributed equally: Chun-fen Mo, Jun Li, Shu-xia Yang

Authors and Affiliations

  1. Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, China

    Chun-fen Mo, Shu-xia Yang, Hui-jie Guo, Yang Liu, Xing-yan Luo, Yan-tang Wang, Min-hui Li & Qiang Zou

  2. Department of Gastroenterology, The first affiliated hospital of Chengdu medical college, Chengdu, China

    Jun Li

  3. Department of Urology, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China

    Jing-yi Li

  4. School of Biological Sciences and Technology, Chengdu Medical College, Chengdu, China

    Jing-yi Li

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Contributions

C.F.M., J.L. and S.X.Y. designed the project and performed all the experiments. H.J.G. and X.Y.L. helped to conduct animal experiments. J.L. and Y.T.W. provided clinical samples. C.F.M. wrote the manuscript. C.F.M., S.X.Y., Y.L. and M.H.L. interpreted data and revised the manuscript. J.Y.L. and Q.Z. supervised the research.

Corresponding authors

Correspondence to Chun-fen Mo, Jing-yi Li or Qiang Zou.

Ethics declarations

Ethics approval and consent to participate

Tumour tissues samples were collected from HCC patients who underwent surgical resection at the First Affiliated Hospital of Chengdu Medical College (Chengdu, China). The patients agreed to enter the study and signed the informed consent. This study was approved by the Committee for Ethical Review of Research involving Human Subjects of the First Affiliated Hospital of Chengdu Medical College and was performed in accordance with the Declaration of Helsinki. The clinical pathological information of HCC patients was summarised in Table 1. All animal experiments were performed in accordance with relevant guidelines and regulations and approved by the Institutional Animal Care and Use Committee of Chengdu Medical College.

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Not applicable.

Data availability

The datasets generated and/or analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Funding information

This study was supported by the National Natural Science Foundation of China (81402944, 81702446, 81871300), Application and Basic Project of Science and Technology Department of Sichuan Province (2018JY0440, 2017JY0174) and Research Fund of Chengdu Medical College (CYZ16-01).

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Mo, Cf., Li, J., Yang, Sx. et al. IQGAP1 promotes anoikis resistance and metastasis through Rac1-dependent ROS accumulation and activation of Src/FAK signalling in hepatocellular carcinoma. Br J Cancer 123, 1154–1163 (2020). https://doi.org/10.1038/s41416-020-0970-z

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