Research ArticleCell Biology

The depalmitoylase APT1 directs the asymmetric partitioning of Notch and Wnt signaling during cell division

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Sci. Signal.  02 Jan 2018:
Vol. 11, Issue 511, eaam8705
DOI: 10.1126/scisignal.aam8705

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Lipid modification promotes cancer cell heterogeneity

Asymmetric cell division generates daughter cells that have distinct fates and is accomplished through the unequal distribution of cell fate determinants or signaling pathway components. Stypulkowski et al. found that the depalmitoylase APT1 was asymmetrically localized in dividing cancer cells, and its catalytic activity was required for asymmetric localization of the Notch antagonist Numb and the Wnt signaling mediator β-catenin, both of which are palmitoylated. The polarity complex component CDC42 was required for the asymmetric localization of both APT1 and β-catenin. APT1-mediated asymmetric partitioning of Numb and β-catenin restricted Notch and Wnt signaling to one daughter cell or the other, induced a mammary stem cell transcriptional signature in breast cancer cells, and promoted heterogeneity and self-renewal capacity in breast cancer cells. These results identify palmitoylation-dependent asymmetric partitioning of cell fate determinants as a potential driver of tumor cell heterogeneity, which has been associated with tumor progression and metastatic potential.