Targeting CK2 as a multi-potential anti-cancer strategy (DSB.AD001.105)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of neuroscience (IN)

Project manager

LORENZOALBERTO PINNA
Phone number: 049 8276108
Email: lorenzo.pinna@unipd.it

Abstract

Protein kinase CK2 is a ubiquitous, pleiotropic Ser/Thr protein kinase whose over-expression in many tumour cells critically
contributes to their survival through a "non oncogene addiction" mechanism. CK2 is implicated in many of the cell biology
phenomena associated with cancer and it plays a "lateral" role in an ample spectrum of signal transduction pathways whose
dysregulation leads to malignancy, reinforcing the concept that targeting CK2 may represent a general strategy to treat neoplasia
in different contexts.. A wide variety of cell permeable CK2 inhibitors have been developed, one of which, CX-4945, is already
in clinical trials. A dual inhibitor (TDB) hitting both CK2 and PIM-1, displays toward cancer cells a cytotoxic efficacy more
pronounced than CX-4945 and already passed a tolerability test on mice. While attempts to generate tumour cells entirely
deprived of CK2 failed, viable fibroblast cell lines where both catalytic subunits of CK2 have been knocked out by the
CRISPR/Cas9 technology have been generated in our lab.

Goals

- Identificare eventi CK2-dipendenti che costituiscano "hallmarks" del cancro
- Identificare proteine la cui espressione/fosforilazione è alterata in cellule KO per CK2
- Ideare e sviluppare nuove strategie di targeting di CK2, in particolare in modelli di glioblastoma, che siano efficaci anche in cellule farmacoresistenti
- Discriminare tra effetti specifici e aspecifici di inibitori di CK2
- Fosforilazione del "secretoma": meccanismi e significato

Start date of activity

02/01/2017

Keywords

kinase, phoshorylation, signal transduction inhibitors

Last update: 04/12/2023