Journal article

Combining High-Content Imaging and Phenotypic Classification Analysis of Senescence-Associated Beta-Galactosidase Staining to Identify Regulators of Oncogene-Induced Senescence

Keefe T Chan, Lassi Paavolainen, Katherine M Hannan, Amee J George, Ross D Hannan, Kaylene J Simpson, Peter Horvath, Richard B Pearson

ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES | MARY ANN LIEBERT, INC | Published : 2016

Abstract

Hyperactivation of the PI3K/AKT/mTORC1 signaling pathway is a hallmark of the majority of sporadic human cancers. Paradoxically, chronic activation of this pathway in nontransformed cells promotes senescence, which acts as a significant barrier to malignant progression. Understanding how this oncogene-induced senescence is maintained in nontransformed cells and conversely how it is subverted in cancer cells will provide insight into cancer development and potentially identify novel therapeutic targets. High-throughput screening provides a powerful platform for target discovery. Here, we describe an approach to use RNAi transfection of a pre-established AKT-induced senescent cell population a..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia program grant


Awarded by Cancer Council Victoria


Awarded by TEKES FiDiPro Fellow Grant


Funding Acknowledgements

This work was supported by a National Health and Medical Research Council (NHMRC) of Australia program grant (1053792) and a Cancer Council Victoria Grant-in-Aid (1065118). The Victorian Centre for Functional Genomics (VCFG) is funded by the Australian Cancer Research Foundation (ACRF); the Victorian Department of Industry, Innovation and Region Development (DIIRD); the Australian Phenomics Network (APN) and supported by funding from the Australian Government Education Investment Fund through the Super Science Initiative; the Australasian Genomics Technologies Association (AGTA); the Brockhoff Foundation; and the Peter MacCallum Cancer Centre Foundation. L.P. and P.H. are supported by a TEKES FiDiPro Fellow Grant 40294/13. R.D.H and R.B.P are funded by NHMRC Fellowships. P.H. acknowledges the Hungarian National Brain Research Program (MTA-SE-NAP B-BIOMAG). The authors thank Daniel Thomas and Jennii Luu (VCFG) for their expert technical assistance.