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Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous carcinoma in which various tumor-suppressor genes are lost by mutation, deletion, or silencing. Here we report a tumor-suppressive mode of action for growth-differentiation factor 11 (GDF11) and an unusual mechanism of its inactivation in TNBC. GDF11 promotes an epithelial, anti-invasive phenotype in 3D triple-negative cultures and intraductal xenografts by sustaining expression of E-cadherin and inhibitor of differentiation 2 (ID2). Surprisingly, clinical TNBCs retain the GDF11 locus and expression of the protein itself. GDF11 bioactivity is instead lost because of deficiencies in its convertase, proprotein convertase subtilisin/kexin type 5 (PCSK5), causing inactive GDF11 precursor to accumulate intracellularly. PCSK5 reconstitution mobilizes the latent TNBC reservoir of GDF11 in vitro and suppresses triple-negative mammary cancer metastasis to the lung of syngeneic hosts. Intracellular GDF11 retention adds to the concept of tumor-suppressor inactivation and reveals a cell-biological vulnerability for TNBCs lacking therapeutically actionable mutations.
Pubmed ID: 29161592 RIS Download
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View all literature mentionsCommercial antibody vendor which supplies antibodies and other products to life science researchers.
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View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsMus musculus with name BALB/cAnNCrl from IMSR.
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Mus musculus with name CB17.Cg-PrkdcscidLyst
Cell line NMuMG is a Spontaneously immortalized cell line with a species of origin Mus musculus
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View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
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View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis monoclonal targets Raised against amino acids 1-552 representing full length Smad4 of human origin
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View all literature mentionsSoftware that provides an integrated solution for the Illumina microarray data analysis.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsThis monoclonal targets V5 Tag
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View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThis polyclonal targets FLAG
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View all literature mentionsCell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets FLAG
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Mus musculus with name CB17.Cg-PrkdcscidLyst
This polyclonal targets V5 Tag
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View all literature mentionsMus musculus with name BALB/cAnNCrl from IMSR.
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Vinculin clone V284
View all literature mentionsThis monoclonal targets Raised against amino acids 1-552 representing full length Smad4 of human origin
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsCell line MCF10DCIS.com is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
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View all literature mentionsThis polyclonal targets MAPK14
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Mus musculus with name CB17.Cg-PrkdcscidLyst
This polyclonal targets p44/42 MAPK (Erk1/2)
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View all literature mentionsThis polyclonal targets FLAG
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View all literature mentionsThis monoclonal targets JUND
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Mapk14
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View all literature mentionsThis monoclonal targets Phospho-Smad1 (Ser463/465)/ Smad5 (Ser463/465)/ Smad9 (Ser465/467)
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View all literature mentionsThis recombinant monoclonal targets Smad3 (phospho S423 + S425)
View all literature mentionsThis recombinant monoclonal targets Smad3 (phospho S423 + S425)
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View all literature mentionsThis polyclonal targets Phospho-Smad2 (Ser465/467)
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View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
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View all literature mentionsThis monoclonal targets BMP11 antibody [EPR4567(2)]
View all literature mentionsThis monoclonal targets GM130
View all literature mentionsThis monoclonal targets Human GDF11
View all literature mentionsThis monoclonal targets BMP11 antibody [EPR4567(2)]
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