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Multiple cancer-related genes both promote and paradoxically suppress growth initiation, depending on the cell context. We discover an explanation for how this occurs for one such protein, Stat3, based on asymmetric cell division. Here, we show that Stat3, by Stathmin/PLK-1, regulates mitotic spindle orientation, and we use it to create and test a model for differential growth initiation. We demonstrate that Integrin-α6 is polarized and required for mammary growth initiation. Spindles orient relative to polar Integrin-α6, dividing perpendicularly in normal cells and parallel in tumor-derived cells, resulting in asymmetric or symmetric Integrin-α6 inheritance, respectively. Stat3 inhibition randomizes spindle orientation, which promotes normal growth initiation while reducing tumor-derived growth initiation. Lipid raft disruption depolarizes Integrin-α6, inducing spindle-orientation-independent Integrin-α6 inheritance. Stat3 inhibition no longer affects the growth of these cells, suggesting Stat3 acts through the regulation of spindle orientation to control growth initiation.
Pubmed ID: 32187533
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Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis polyclonal targets NUMB
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Integrin alpha6 (F-6)
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis monoclonal targets PLK1 (pT210)
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View all literature mentionsThis monoclonal targets Histone H3, phospho (Ser10)
View all literature mentionsThis monoclonal targets CD49f
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View all literature mentionsThis polyclonal targets FAK, phospho (Tyr576)
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View all literature mentionsThis monoclonal targets CD29 (Integrin β1 chain)
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View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis monoclonal targets Stmn1
View all literature mentionsThis monoclonal targets CD49f
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Human PLK1
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets GAPDH
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis monoclonal targets CD326
View all literature mentionsThis monoclonal targets Integrin beta1 clone 6S6
View all literature mentionsThis polyclonal targets Pericentrin
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsCell line HeLa Kyoto is a Cancer cell line with a species of origin Homo sapiens (Human)
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 mentionsCell line C2BBe1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsSoftware for image capture, processing and analysis with Leica fluorescence and confocal microscopes.
View all literature mentionsCell line EO771 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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