Abstract

induced tumours in vivo. At the cellular level, using mouse embryonic fibroblasts (MEFs), we demonstrate that Cep55 overexpression induces proliferation advantage by modulating multiple cellular signalling networks including the hyperactivation of the Pi3k/Akt pathway. Notably, Cep55 overexpressing MEFs have a compromised Chk1-dependent S-phase checkpoint, causing increased replication speed and DNA damage, resulting in a prolonged aberrant mitotic division. Importantly, this phenotype was rescued by pharmacological inhibition of Pi3k/Akt or expression of mutant Chk1 (S280A) protein, which is insensitive to regulation by active Akt, in Cep55 overexpressing MEFs. Moreover, we report that Cep55 overexpression causes stabilized microtubules. Collectively, our data demonstrates causative effects of deregulated Cep55 on genome stability and tumorigenesis which have potential implications for tumour initiation and therapy development.

Authors	Sinha, Debottam; Nag, Purba; Nanayakkara, Devathri; Duijf, Pascal H G; Burgess, Andrew; Raninga, Prahlad; Smits, Veronique A J; Bain, Amanda L; Subramanian, Goutham; Wall, Meaghan; Finnie, John W; Kalimutho, Murugan; Khanna, Kum Kum
Journal	Communications Biology
Pages	593
Volume	3
Date	1/10/2020
Grant ID
Funding Body	Griffith University International Postgraduate Research Scholarship (GUIPRS)
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s42003-020-01304-6