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bioRxiv · 10.1101/2022.12.12.520127

Cell polarity opposes Jak-STAT mediated Escargot activation that drives intratumor heterogeneity in a Drosophila tumor model

Chatterjee, D.·Cong, F.·Wang, X.-F.·Costa, C. A. M.·Huang, Y.-C.·Deng, W.-M.
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Abstract

In proliferating neoplasms, microenvironment-derived selective pressures promote tumor heterogeneity by imparting diverse capacities for growth, differentiation and invasion. However, what makes a tumor cell respond to signaling cues differently from a normal cell is not well understood. In the Drosophila ovarian follicle cells, apicobasal-polarity loss induces heterogenous epithelial multilayering. When exacerbated by oncogenic-Notch expression, this multilayer displays an increased consistency in the occurrence of morphologically distinguishable cells adjacent to the polar follicle cells. Polar cells release the Jak-STAT ligand Unpaired (Upd), in response to which, neighboring polarity-deficient cells exhibit a precursor-like transcriptomic state. Using single-cell transcriptomics, we discovered the ectopic activation of the Snail-family transcription factor Escargot (Esg) in these cells. We also characterized similar relationship between Upd and Esg during early follicular development, where the establishment of polarity determines follicle-cell differentiation. Overall, our results indicate that epithelial-cell polarity acts as a gatekeeper against microenvironmental selective pressures that drive heterogeneity.

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Chatterjee, D., Cong, F., Wang, X.-F., Costa, C. A. M., Huang, Y.-C., Deng, W.-M.. 2022-12-14. Cell polarity opposes Jak-STAT mediated Escargot activation that drives intratumor heterogeneity in a Drosophila tumor model. https://doi.org/10.1101/2022.12.12.520127

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