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Family-Wide Photoproximity Profiling of Integrin Protein Social Networks in Cancer
Anthony J Carlos1, Dongbo Yang1, Deborah M Thomas1
1Department of Chemistry, The University of Chicago. Chicago, IL, 60637, USA.
Biorxiv : the Preprint Server for Biology
|September 30, 2024
Summary
Researchers developed a new method to map protein interactions around integrins in live cells. This technique identifies protein networks that can serve as markers for cell identity and cancer progression, particularly in triple-negative breast cancer.
Area of Science:
- Cellular Biology
- Biochemistry
- Molecular Interactions
Background:
- Integrin receptors are crucial for cell communication with their environment, regulating vital cellular processes.
- Understanding integrin-mediated protein interactions is key, but current methods face limitations in spatial and temporal resolution.
- Detecting dynamic binding partners of integrins in native conditions remains a significant challenge.
Purpose of the Study:
- To develop a novel method for detecting and quantifying integrin-centered protein interaction networks in live cells and tissues.
- To create quantitative maps of these protein networks across different cell types and microenvironments.
- To identify specific protein interaction patterns associated with cancer cell states and patient outcomes.
Main Methods:
- Developed an integrin-family-directed quantitative photoproximity protein interaction (PhotoPPI) profiling method.
- Applied PhotoPPI to detect and quantify native integrin-centered protein networks without genetic modification or antibodies.
- Analyzed integrin-centered protein networks in various cancer cell lines and triple-negative breast cancer (TNBC) cells.
Main Results:
- Generated quantitative maps of integrin-centered protein social networks, revealing conserved and unique binding partners.
- Identified specific AND-gate binding partners in cancer cells linked to migration, microenvironmental interactions, and proliferation, correlating with metastatic state.
- Discovered unique protein expression 'barcodes' around integrins in TNBC cells that predict disease progression and patient outcomes.
Conclusions:
- The PhotoPPI method provides high-resolution, family-wide maps of native protein interactors on live cells.
- Integrin-centered protein networks function as dynamic AND-gate markers for cell identity, microenvironmental context, and disease state.
- These findings offer new insights into cancer biology and potential biomarkers for TNBC patient stratification.
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