Src family kinases (SFKs) are evolutionarily conserved proteins acting downstream of receptors and regulating cellular processes including proliferation, adhesion, and migration. Elevated SFK expression and activity correlate with progression of a variety of cancers. Here, using the Drosophila melanogaster border cells as a model, we report that localized activation of a Src kinase promotes an unusual behavior: engulfment of one cell by another. By modulating Src expression and activity in the border cell cluster, we found that increased Src kinase activity, either by mutation or loss of a negative regulator, is sufficient to drive one cell to engulf another living cell. We elucidate a molecular mechanism that requires integrins, the kinases SHARK and FAK, and Rho family GTPases, but not the engulfment receptor Draper. We propose that cell cannibalism is a result of aberrant phagocytosis, where cells with dysregulated Src activity fail to differentiate between living and dead or self versus non-self, thus driving this malignant behavior.
Activated Src kinase promotes cell cannibalism in Drosophila
Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. A.Y. Torres reported a patent to GENETICALLY ENGINEERED PHAGOCYTES, AND RELATED COMPOSITIONS, VECTORS, METHODS, AND SYSTEMS pending. D.J. Montell reported other from Inceptor Bio outside the submitted work; in addition, D.J. Montell had a patent to 17/995,083 pending “Inceptor Bio.” No other disclosures were reported.
- Award Id(s): R01GM046425
Alba Yurani Torres, Maddalena Nano, Joseph P. Campanale, Sierra Deak, Denise J. Montell; Activated Src kinase promotes cell cannibalism in Drosophila. J Cell Biol 6 November 2023; 222 (11): e202302076. doi: https://doi.org/10.1083/jcb.202302076
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