MCL-1 is a prognostic indicator and drug target in breast cancer

Campbell, K. J. et al. (2018) MCL-1 is a prognostic indicator and drug target in breast cancer. Cell Death and Disease, 9, 19. (doi: 10.1038/s41419-017-0035-2) (PMID:29339815) (PMCID:PMC5833338)

Abstract

Analysis of publicly available genomic and gene expression data demonstrates that MCL1 expression is frequently elevated in breast cancer. Distinct from other pro-survival Bcl-2 family members, the short half-life of MCL-1 protein led us to investigate MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data. Here, we report associations between high MCL-1 and poor prognosis in specific subtypes of breast cancer including triple-negative breast cancer, an aggressive form that lacks targeted treatment options. Deletion of MCL-1 in the mammary epithelium of genetically engineered mice revealed an absolute requirement for MCL-1 in breast tumorigenesis. The clinical applicability of these findings was tested through a combination of approaches including knock-down or inhibition of MCL-1 to show triple-negative breast cancer cell line dependence on MCL-1 in vitro and in vivo. Our data demonstrate that high MCL-1 protein expression is associated with poor outcome in breast cancer and support the therapeutic targeting of MCL-1 in this disease.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dickson, Ms Ashley and Campbell, Dr Kirsteen and Blyth, Professor Karen and Kalna, Dr Gabriela and Tait, Professor Stephen and Ferrari, Mr Nicola and Edwards, Professor Joanne and Mason, Miss Susan and Johnson, Ms Emma and Ryan, Professor Kevin
• Authors: Campbell, K. J., Dhayade, S., Ferrari, N., Sims, A. H., Johnson, E., Mason, S. M., Dickson, A., Ryan, K. M., Kalna, G., Edwards, J., Tait, S. G.W., and Blyth, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine; College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Cell Death and Disease
• Publisher: Nature Publishing Group
• ISSN: 2041-4889
• ISSN (Online): 2041-4889
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Cell Death and Disease 9:19
• Publisher Policy: Reproduced under a Creative Commons License