Journal article

Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone

Katie L Owen, Linden J Gearing, Damien J Zanker, Natasha K Brockwell, Weng Hua Khoo, Daniel L Roden, Marek Cmero, Stefano Mangiola, Matthew K Hong, Alex J Spurling, Michelle McDonald, Chia-Ling Chan, Anupama Pasam, Ruth J Lyons, Hendrika M Duivenvoorden, Andrew Ryan, Lisa M Butler, John M Mariadason, Tri Giang Phan, Vanessa M Hayes Show all

EMBO reports | WILEY | Published : 2020

Abstract

The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor-intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor-intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, pr..

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Grants

Awarded by Australian Research Council Future Fellowship


Awarded by Victorian Cancer Agency Mid-career fellowship


Funding Acknowledgements

The authors thank the patients who donated material for this study and the efforts of all Biobank staff. This project is supportesd by grant funding from the Prostate Cancer Foundation of Australia and Movember (Movember Revolutionary Team Award) to P.I.C., B.S.P., C.H., N.C., A.S., and V.M.H., and Fellowship funding to B.S.P. (Australian Research Council Future Fellowship, FT130100671; Victorian Cancer Agency Mid-career fellowship, MCRF16022).