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Interaction between laminin-5γ2 and integrin β1 promotes the tumor budding of colorectal cancer via the activation of Yes-associated proteins

Oncogene volume 39, pages 1527–1542 (2020)Cite this article

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A Correction to this article was published on 12 August 2022

A Correction to this article was published on 04 December 2019

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Abstract

Colorectal cancer (CRC) is a common cancer type and a threat to human health. Tumor budding (TB) is the presence of a single cancer cell or clusters of up to five cancer cells prior to the invasive front of an aggressive carcinoma and is an independent prognosis factor for CRC. The molecular mechanism of TB is still unclear, and drugs that inhibit this process are still in the blank stage. This study found that TBs exhibit characteristics of partial EMT with a decreased expression of E-cadherin and no substantial differences in the expression of N-cadherin and vimentin. We also observed the interaction of integrin with extracellular matrix components, laminin-5γ2 (LN-5γ2), play essential roles in the TB of CRC. We then verified that the interaction between LN-5γ2 and integrin β1 promotes the TB of CRC via the activation of FAK and Yes-associated proteins (YAP). A natural drug monomer, cucurbitacin B, was screened using virtual screening methods for the interaction interface of proteins. We found that this monomer could block the interaction interface between LN-5γ2 and integrin β1 and substantially inhibit the TB of CRC cells via inactivation of YAP. This study provides new insights into the mechanism of TB mechanism and the development of drugs targeting the TB of CRC.

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Acknowledgements

This work was funded by the following: National Natural Science Funds of China (81972629, 81802945, 81872374, and 81572838), the Taishan Scholar Project Special Funding and the National Science and Technology Major Project (2018ZX09736-005).

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  1. These authors contributed equally: Bijiao Zhou, Shumin Zong, Weilong Zhong

Authors and Affiliations

  1. Molecular Pathology Institute of Gastrointestinal Tumors, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029, Shandong, China

    Bijiao Zhou, Renya Zhang, Lei Li, Wei Wang & Yanrong Liu

  2. State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China

    Bijiao Zhou, Shumin Zong, Yixuan Tian, Lumeng Wang, Qian Zhang, Xin Chen, Yaju Feng, Binghui Zhai, Tao Sun & Yanrong Liu

  3. Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China

    Bijiao Zhou, Shumin Zong, Yixuan Tian, Lumeng Wang, Qian Zhang, Xin Chen, Yaju Feng, Binghui Zhai, Tao Sun & Yanrong Liu

  4. Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China

    Weilong Zhong

  5. Department of Pathology, Hospital of Shun Yi District, Beijing, China

    Jianmin Zhao

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Zhou, B., Zong, S., Zhong, W. et al. Interaction between laminin-5γ2 and integrin β1 promotes the tumor budding of colorectal cancer via the activation of Yes-associated proteins. Oncogene 39, 1527–1542 (2020). https://doi.org/10.1038/s41388-019-1082-1

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