From PICH regulation to tumor phenotypes: exploring the functional role of CIP2A

PhD defence by Alisha Akhilesh Shah

Assessment Committee

Associate professor Claus Storgaard Sørensen, Biotech Research and Innovation Centre (BRIC), University of Copenhagen (Chairperson)
Associate professor Paolo Ceppi, University of Southern Denmark
Professor Fumiko Esashi, University of Oxford

Supervisors

Professor Marja Jaattela
Professor Ying Liu
Guest Researcher Victoria Alexandra Bjerregaard
PhD, Senior Scientific Manager Pietri Kullervo Puustinen

Department

Department of Cellular and Molecular Medicine

Graduate Programme

Cellular and Genetic Medicine

Place

Building: Danish Cancer Institute, Room: 7.2.A.B (Biografen), Strandboulevarden 49, 2100 Copenhagen

Email address to gain access to the thesis: alisha.a.shah@gmail.com.
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Short description of the thesis

Genome instability is a hallmark of cancer. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein overexpressed in most cancers and increasingly linked to genome stability in mitosis. This PhD thesis identifies a novel role for CIP2A in regulating PICH, a protein that resolves ultrafine DNA bridges arising from replication stress. CIP2A regulates PLK1 signalling and the timing of PICH phosphorylation, and its loss impairs bridge processing and increases micronuclei formation.
Furthermore, to support the development of small-molecule inhibitors against CIP2A, this thesis examined the effects of CIP2A loss in gastrointestinal cancer cell lines, where it affected growth, invasion, and nucleolar transcription. Together, these findings support CIP2A as a promising target for cancer therapy.