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

Kirsteen J Campbell, Sandeep Dhayade, Nicola Ferrari, Andrew H. Sims, Emma Johnson, Susan M Mason, Ashley Dickson, Kevin M Ryan, Gabriela Kalna, Joanne Edwards, Stephen W.G. Tait, Karen Blyth

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number19
Number of pages14
JournalCell Death and Disease
Volume9
DOIs
Publication statusPublished - 16 Jan 2018

Keywords

  • MCL-1
  • Breast Cancer
  • Therapy
  • Apoptosis
  • BH3-mimetic

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