The JNK and Hippo pathways control epithelial integrity and prevent tumor initiation by regulating an overlapping transcriptome

Katrina A Mitchell; Joseph HA Vissers; Jonathan M Pojer; Elliot Brooks; Abdul Jabbar Saiful Hilmi; Anthony T Papenfuss; Jan Schroder; Kieran F Harvey

Journal article

The JNK and Hippo pathways control epithelial integrity and prevent tumor initiation by regulating an overlapping transcriptome

Katrina A Mitchell, Joseph HA Vissers, Jonathan M Pojer, Elliot Brooks, Abdul Jabbar Saiful Hilmi, Anthony T Papenfuss, Jan Schroder, Kieran F Harvey

Current Biology | Cell Press | Published : 2024

DOI: 10.1016/j.cub.2024.07.060

Abstract

Epithelial organs maintain their integrity and prevent tumor initiation by actively removing defective cells, such as those that have lost apicobasal polarity. Here, we identify how transcription factors of two key signaling pathways—Jun-N-terminal kinase (JNK) and Hippo—regulate epithelial integrity by controlling transcription of an overlapping set of target genes. Targeted DamID experiments reveal that, in proliferating cells of the Drosophila melanogaster eye, the AP-1 transcription factor Jun and the Hippo pathway transcription regulators Yorkie and Scalloped bind to a common suite of target genes that promote organ growth. In defective neoplastic cells, AP-1 transcription factors repre..

View full abstract

University of Melbourne Researchers

Katrina Mitchell Author

Joep Vissers Author

Tony Papenfuss Author

Kieran Harvey Author

Related Projects (3)

CONTROL OF ORGAN SIZE AND CANCER BY THE HIPPO PATHWAY

The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim ..

The Hippo pathway in development and cancer

Appropriate growth of organs is essential for life and can go awry in diseases such as cancer. A crucial regulator of organ size and cancer ..

HOW DO NEURONS MAINTAIN THEIR FATE?

This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintena..

Grants

Awarded by Australian Research Council

Awarded by Senior Research Fellowship

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by NHMRC Senior Research Fellowship

Funding Acknowledgements

We thank members of the Harvey lab for discussions. We thank I. Hariharan,B. Hay, H. Richardson, the Bloomington Drosophila Stock Center, the Vienna DrosophilaRNAi Center, the Australian Drosophila Research Support Facility (www.ozdros.com ), and the Developmental Studies Hybridoma Bank for D. melanogaster stocks and antibodies. This research was supported by the Australian Research Council (DP180102044, DP190101743, and DP230101406) . K.F.H. was supported by a Senior Research Fellowship (1078220) and Investigator grant (1194467) from the National Health and Medical Research Council of Australia (NHMRC) , K.A.M. and J.M.P. were supported by Australian Postgraduate Awards, and A.T.P. was supported by an NHMRC Senior Research Fellowship (1116955) and the Lorenzo and Pamela Galli Medical Research Trust. This research benefited from support from the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support. We acknowledge the Peter Mac Centre for Advanced Histology and Microscopy and the Molecular Genomics Core Facility and support to them from the Peter MacCallum Cancer Foundation and the Australian Cancer Research Foundation.