Hippo-TOR Signaling Crosstalks Underpin Microtubule Acetylation-linked Carcinogenesis in Drosophila Squamous Epithelia
Bhattacharya, R.; SINHA, P.; Mohan, N.
Show abstract
Protooncogenes, which can also function as tumor suppressors, are termed double agents. The Hippo pathway transcriptional coactivators YAP/TAZ and their Drosophila homolog Yorkie (Yki) are known oncogenes. Paradoxically, in squamous epithelia, they are constitutively active yet non-oncogenic and can even function as tumor suppressors. We previously found that loss of Yki in the Drosophila male accessory gland (MAG) squamous epithelium promotes squamous cell carcinoma (SCC) by upregulating TOR signaling, but the mechanism was unknown. Here, we show that this tumorigenesis stems from TOR-mediated hyperacetylation of -tubulin. This pathway is tissue-specific, as the ovarian follicular epithelium is resistant to Yki loss. A comparison of MAG and follicular epithelia single-cell transcriptomic data revealed their distinct Yki-TOR signaling states, suggesting lineage-specific mechanoconstraints in these two lineages. Our results identify suppression of TOR-driven -tubulin acetylation as the mechanistic basis for Ykis role as a double-agent in select squamous epithelia.
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