Comprehensive Proteomic Characterization Reveals Subclass-Specific Molecular Aberrations within Triple-negative Breast Cancer
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Published on: March 20, 2020
Max Kosok1, Asfa Alli-Shaik2, Boon Huat Bay3
1Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.
Abstract:
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer lacking targeted therapies. This is attributed to its high heterogeneity that complicates elucidation of its molecular aberrations. Here, we report identification of specific proteome expression profiles pertaining to two TNBC subclasses, basal A and basal B, through in-depth proteomics analysis of breast cancer cells. We observed that kinases and proteases displayed unique expression patterns within the subclasses. Systematic analyses of protein-protein interaction and co-regulation networks of these kinases and proteases unraveled dysregulated pathways and plausible targets for each TNBC subclass. Among these, we identified kinases AXL, PEAK1, and TGFBR2 and proteases FAP, UCHL1, and MMP2/14 as specific targets for basal B subclass, which represents the more aggressive TNBC cell lines. Our study highlights intricate mechanisms and distinct targets within TNBC and emphasizes that these have to be exploited in a subclass-specific manner rather than a one-for-all TNBC therapy.
Insights
Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies. This study identifies distinct proteome profiles and specific therapeutic targets for basal A and basal B TNBC subclasses.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype.
- TNBC lacks targeted therapies due to its molecular heterogeneity.
- Subclassification of TNBC is crucial for developing effective treatments.
Purpose of the Study:
- To identify distinct proteome expression profiles for TNBC subclasses.
- To uncover subclass-specific molecular aberrations and therapeutic targets.
- To differentiate therapeutic strategies for basal A and basal B TNBC.
Main Methods:
- In-depth proteomics analysis of breast cancer cells.
- Identification of proteome expression profiles for TNBC subclasses.
- Analysis of protein-protein interaction and co-regulation networks.
Main Results:
- Kinases and proteases show unique expression patterns in basal A and basal B TNBC.
- Dysregulated pathways and plausible targets were identified for each subclass.
- Specific targets for the aggressive basal B subclass include kinases AXL, PEAK1, TGFBR2 and proteases FAP, UCHL1, MMP2/14.
Conclusions:
- TNBC exhibits intricate molecular mechanisms that vary between subclasses.
- Therapeutic strategies for TNBC should be subclass-specific.
- Targeting specific kinases and proteases offers potential for basal B TNBC treatment.
