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Integrin β4 Regulates Cell Migration of Lung Adenocarcinoma Through FAK Signaling

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Abstract

The role of the integrin family in malignancy has received increasing attention. Many studies have confirmed that ITGB4 could activate multiple signal pathways and promote cell migration in various cancers. However, the regulatory role of integrin β4 (ITGB4) in lung adenocarcinoma (LUAD) is still unclear. Examination of the expression or survival analysis of ITGB4 in cells, pathological samples, and bioinformatics lung adenocarcinoma databases showed ITGB4 was highly expressed in LUAD and significantly associated with poor prognosis. Small interfering RNA and plasmids were performed to investigate the effect of changes in ITGB4 expression on lung adenocarcinoma. Focal adhesion kinase (FAK) inhibitor defactinib was used to further explore the molecular mechanism of ITGB4. The results showed depletion of ITGB4 inhibited migration and activation of FAK signaling pathways in lung adenocarcinoma cells. Moreover, increased ITGB4 expression activated FAK signaling and promoted cell migration, which can be reversed by defactinib. In addition, ITGB4 could interact with FAK in lung adenocarcinoma cells. ITGB4 may promote cell migration of lung adenocarcinoma through FAK signaling pathway and has the potential to be a biomarker for lung adenocarcinoma.

Graphical Abstract

Integrin β4 (ITGB4), Focal adhesion kinase (FAK), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression and Broad Institute Cancer Cell Line Encyclopedia (CCLE), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Co- immunoprecipitation (Co-IP).

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Data Availability

The datasets collected and analyzed during the study are available in the TCGA, Gene Expression Omnibus (GSE26939 and GSE72094 cohorts), and The Genotype-Tissue Expression and Broad Institute Cancer Cell Line Encyclopedia (CCLE) databases. The other data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical issues.

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Acknowledgements

We acknowledge the GEO, TCGA, CCLE, and GTEx databases for free use.

Funding

This work was supported by the Natural Science Foundation of Hebei Province (No. H2021108003).

Author information

Author notes

  1. Shusen Zhang, Chengyu Liu and Dengxiang Liu have contributed equally to this work.

Authors and Affiliations

  1. Hebei Province Xingtai People’s Hospital Postdoctoral Workstation, Xingtai, China

    Shusen Zhang & Shubo Chen

  2. Postdoctoral Mobile Station, Hebei Medical University, Shijiazhuang, China

    Shusen Zhang & Zhigang Cai

  3. Department of Pulmonary and Critical Care Medicine, Affiliated Xing Tai People Hospital of Hebei Medical University, Xingtai, China

    Shusen Zhang, Xuecong Ning & Ping Zhang

  4. The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China

    Shusen Zhang & Zhigang Cai

  5. Department of Surgery, Graduate School of Hebei Medical University, Shijiazhuang, China

    Chengyu Liu

  6. Department of Oncology, Affiliated Xing Tai People Hospital of Hebei Medical University, Xingtai, China

    Dengxiang Liu, Hui Li, Xiaochong Zhang & Shubo Chen

  7. Department of Anesthesiology, Affiliated Xing Tai People Hospital of Hebei Medical University, Xingtai, China

    Yuanyuan Lu

  8. Heibei Key Laboratory of Respiratory Critical Care, Shijiazhuang, China

    Zhigang Cai

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  1. Shusen Zhang
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Contributions

Conceptualization: SC and ZC; Writing and original draft preparation: SZ, CL, and DL; Data processing and analysis: SZ, CL, XN, HL, and PZ; Immunohistochemistry assays and analysis: SZ, XZ, and YL; Cell and western blot experiments: SZ, CL, DL, and HL; Supervision and project administration: SC and ZC; Review and editing of the manuscript: SC, ZC, and DL.

Corresponding authors

Correspondence to Shubo Chen or Zhigang Cai.

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Conflict of interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical Approval

The study was approved by the Ethics Committee of affiliated Xing Tai People Hospital of Hebei Medical University. All methods in this study were performed in accordance with the relevant guidelines and regulations. The study is reported in accordance with ARRIVE guidelines.

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Zhang, S., Liu, C., Liu, D. et al. Integrin β4 Regulates Cell Migration of Lung Adenocarcinoma Through FAK Signaling. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01061-5

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