Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer
- Shengjing Hospital of China Medical University, China
- Dalian University of Technology, China
- Mayo Clinic, United States
Abstract
Background: Integrin family are known as key gears in focal adhesion for triple-negative breast cancer (TNBC) metastasis. However, the integrin independent factor TLN1 remains vague in TNBC.
Methods: Bioinformatics analysis was performed based on TCGA database and Shengjing Hospital cohort. Western blot and RT-PCR were used to detect the expression of TLN1 and integrin pathway in cells. A small-molecule C67399 was screened for blocking TLN1 and integrin β1 through a novel computational screening approach by targeting the protein-protein binding interface. Drug pharmacodynamics were determined through xenograft assay.
Results: Upregulation of TLN1 in TNBC samples correlates with metastasis and worse prognosis. Silencing TLN1 in TNBC cells significantly attenuated the migration of tumour cells through interfering the dynamic formation of focal adhesion with integrin β1, thus regulating FAK-AKT signal pathway and epithelial-mesenchymal transformation. Targeting the binding between TLN1 and integrin β1 by C67399 could repress metastasis of TNBC.
Conclusions: TLN1 overexpression contributes to TNBC metastasis and C67399 targeting TLN1 may hold promise for TNBC treatment.
Funding: This study was supported by grants from the National Natural Science Foundation of China (No. 81872159, 81902607, 81874301), Liaoning Colleges Innovative Talent Support Program (Name: Cancer Stem Cell Origin and Biological Behaviour), Outstanding Scientific Fund of Shengjing Hospital (201803) and Outstanding Young Scholars of Liaoning Province (2019-YQ-10).
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81872159)
- Caigang Liu
Liaoning Colleges Innovative Talent Support Program (Cancer Stem Cell Origin and Biological Behavior)
- Caigang Liu
Outstanding Scientific Fund of Shengjing Hospital (201803)
- Caigang Liu
Outstanding Young Scholars of Liaoning Province (2019-YQ-10)
- Caigang Liu
National Natural Science Foundation of China (81902607)
- Yixiao Zhang
National Natural Science Foundation of China (81874301)
- Yongliang Yang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Renata Pasqualini, Rutgers University, United States
Ethics
Animal experimentation: The current study was approved by the institutional research ethics committee of Shengjing Hospital of China Medical University (Project identification code: 2018PS304K, date on 03/05/2018), and each participant signed an informed consent before being included in the study. Meanwhile, this study was performed in very strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering of the animals, and all the animals were handled according to approved Animal Ethics and Experimentation Committee protocols of Shengjing Hospital of China Medical University (Project identification code: 2018PS312K, date on 03/05/2018).
Human subjects: Written informed consent was obtained from all the patients, and this study was approved by the institutional research ethics committee of China Medical University
Version history
- Received: March 17, 2021
- Accepted: March 7, 2022
- Accepted Manuscript published: March 14, 2022 (version 1)
- Version of Record published: March 21, 2022 (version 2)
Copyright
© 2022, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer
eLife 11:e68481.
https://doi.org/10.7554/eLife.68481
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