Hippo-TOR Signaling Crosstalks Underpin Microtubule Acetylation-linked Carcinogenesis in Drosophila Squamous Epithelia

Abstract

Post-translational modifications (PTM), like acetylation, underpin the functional specialization of the cytoskeleton, such as microtubules (MT). For instance, acetylation of microbules is essential for cell flattening in the Drosophila adult squamous epithelia of female ovarian follicles and male accessory glands (MAG). Here we show that the highly conserved Hippo transcription co-factor Yorkie (Yki), a mechanosensor for cell flattening, regulates the acetylation of MT in squamous epithelia in both these organs. Yet, the fallouts of loss of nuclear Yki signaling are distinct in these two squamous epithelia. Thus, the knockdown of Yki in the squamous epithelia of ovarian follicles compromises their cell flattening. By contrast, knockdown of Yki in the MAG epithelium leads to its cancerous transformation which is suppressed by a simultaneous genetic ablation of MT-acetylation. We further note that Yki-knockdown-induced hyperacetylation of MT in MAG is TOR signaling-dependent. These results reveal that, while Yki-dependent acetylation of MT drives cell flattening, its cell type-specific homeostatic cross-talk with TOR signaling, as in the MAG, when dysregulated, culminates in carcinogenesis.