Hippo effector, Yorkie, is a tumor suppressor in select Drosophila squamous epithelia.

Autor:	Bhattacharya R; Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.; Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India., Kumari J; Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India., Banerjee S; Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.; Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India., Tripathi J; Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.; Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India., Parihar SS; Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.; Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India., Mohan N; Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.; Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India., Sinha P; Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.; Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Sep 24; Vol. 121 (39), pp. e2319666121. Date of Electronic Publication: 2024 Sep 17.
DOI:	10.1073/pnas.2319666121
Abstrakt:	Mammalian Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and Drosophila Yorkie (Yki) are transcription cofactors of the highly conserved Hippo signaling pathway. It has been long assumed that the YAP/TAZ/Yki signaling drives cell proliferation during organ growth. However, its instructive role in regulating developmentally programmed organ growth, if any, remains elusive. Out-of-context gain of YAP/TAZ/Yki signaling often turns oncogenic. Paradoxically, mechanically strained, and differentiated squamous epithelia display developmentally programmed constitutive nuclear YAP/TAZ/Yki signaling. The unknown, therefore, is how a growth-promoting YAP/TAZ/Yki signaling restricts proliferation in differentiated squamous epithelia. Here, we show that reminiscent of a tumor suppressor, Yki negatively regulates the cell growth-promoting PI3K/Akt/TOR signaling in the squamous epithelia of Drosophila tubular organs. Thus, downregulation of Yki signaling in the squamous epithelium of the adult male accessory gland (MAG) up-regulates PI3K/Akt/TOR signaling, inducing cell hypertrophy, exit from their cell cycle arrest, and, finally, culminating in squamous cell carcinoma (SCC). Thus, blocking PI3K/Akt/TOR signaling arrests Yki loss-induced MAG-SCC. Further, MAG-SCCs, like other lethal carcinomas, secrete a cachectin, Impl2-the Drosophila homolog of mammalian IGFBP7-inducing cachexia and shortening the lifespan of adult males. Moreover, in the squamous epithelium of other tubular organs, like the dorsal trunk of larval tracheal airways or adult Malpighian tubules, downregulation of Yki signaling triggers PI3K/Akt/TOR-induced cell hypertrophy. Our results reveal that Yki signaling plays an instructive, antiproliferative role in the squamous epithelia of tubular organs. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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