Proteomics

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Comprehensive proteomic characterization reveals subclass-specific molecular aberrations within triple-negative breast cancer


ABSTRACT: Triple-negative breast cancer (TNBC) is regarded as 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, similar to whole proteome clusters. 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 thus 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Breast, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Asfa Alli Shaik  

LAB HEAD: Jayantha Gunaratne

PROVIDER: PXD017025 | Pride | 2020-03-03

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
191001_BC1_IS1523_bRP.msf Msf
191006_BC1_IS1524_IEF.msf Msf
191030_BC2_IS1526_bRP.msf Msf
191111_BC2_IS1526_IEF.msf Msf
Kosok_Alli-Shaik_et-al.zip Other
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Publications

Comprehensive Proteomic Characterization Reveals Subclass-Specific Molecular Aberrations within Triple-negative Breast Cancer.

Kosok Max M   Alli-Shaik Asfa A   Bay Boon Huat BH   Gunaratne Jayantha J  

iScience 20200128 2


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 subclas  ...[more]

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