Journal article
Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance
MK Walia, PMW Ho, S Taylor, AJM Ng, A Gupte, AM Chalk, ACW Zannettino, TJ Martin, CR Walkley
Elife | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2016
DOI: 10.7554/eLife.13446
Abstract
Mutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-d..
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Awarded by Victorian Cancer Agency
Funding Acknowledgements
[ "National Health and Medical Research Council APP1084230 Mannu K Walia T John Martin Carl R Walkley", "Australian Sarcoma Study Group Johanna Sewell Research Grant Mannu K Walia Carl R Walkley", "Cancer Council Victoria APP1047593 Carl R Walkley", "Cancer Therapeutics CRC PhD Scholarship Alvin JM Ng", "Department of Health, State Government of Victoria Operational Infrastructure Support Scheme T John Martin Carl R Walkley", "Leukaemia Foundation Phillip Desbrow Senior Research Fellowship Carl R Walkley", "National Health and Medical Research Council APP559016 Carl R Walkley", "Victorian Cancer Agency Mid Career Research Fellowship MCRF15015 Carl R Walkley", "The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication." ]