CG7379 and ING1 suppress cancer cell invasion by maintaining cell–cell junction integrity

Rusu, Alexandra D.; Cornhill, Zoe E.; Uribe, Marcos Castellanos; Lourdusamy, Anbarasu; Markus, Zsuzsa; May, Sean T.; Rahman, Ruman; Georgiou, Marios

doi:10.1098/rsob.210077

Authors

Alexandra D. Rusu

Zoe E. Cornhill

Brenda Canales

Marcos Castellanos Uribe

AROCKIA LOURDUSAMY Anbarasu.Lourdusamy@nottingham.ac.uk
Senior Research Fellow

Zsuzsa Markus

Professor SEAN MAY SEAN.MAY@NOTTINGHAM.AC.UK
Professor of Plant Cyber Infrastructure

RUMAN RAHMAN RUMAN.RAHMAN@NOTTINGHAM.AC.UK
Associate Professor

MARIOS GEORGIOU MARIOS.GEORGIOU@NOTTINGHAM.AC.UK
Assistant Professor

Abstract

Approximately 90% of cancer-related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in vivo in Drosophila, reduces the junctional localization of several adherens and septate junction components, and severely disrupts cell-cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion in vitro and disrupts E-cadherin distribution at cell-cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell-cell junction integrity.

Citation

Rusu, A. D., Cornhill, Z. E., Coutiño, B. C., Uribe, M. C., Lourdusamy, A., Markus, Z., …Georgiou, M. (2021). CG7379 and ING1 suppress cancer cell invasion by maintaining cell–cell junction integrity. Open Biology, 11(9), Article 210077. https://doi.org/10.1098/rsob.210077

Journal Article Type	Article
Acceptance Date	Jul 26, 2021
Online Publication Date	Sep 8, 2021
Publication Date	2021-09
Deposit Date	Mar 4, 2022
Publicly Available Date	Mar 7, 2022
Journal	Open Biology
Electronic ISSN	2046-2441
Publisher	The Royal Society
Peer Reviewed	Peer Reviewed
Volume	11
Issue	9
Article Number	210077
DOI	https://doi.org/10.1098/rsob.210077
Keywords	General Biochemistry, Genetics and Molecular Biology; Immunology; General Neuroscience
Public URL	https://nottingham-repository.worktribe.com/output/6398495
Publisher URL	https://royalsocietypublishing.org/doi/10.1098/rsob.210077