HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours

Jeffrey C. Francis, Jennifer R. Gardiner, Yoan Renaud, Ritika Chauhan, Yacob Weinstein, Celso Gomez-Sanchez, Anne Marie Lefrançois-Martinez, Jérôme Bertherat, Pierre Val, Amanda Swain

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background: Understanding the pathways that drive adrenocortical carcinoma (ACC) is essential to the development of more effective therapies. This study investigates the role of the transcription factor HOXB9 and other HOX factors in ACC and its treatment. Methods: We used transgenic mouse models to determine the role of Hoxb9 in adrenal tumour development. Patient transcriptomic data was analysed for the expression of HOX genes and their association with disease. Drug response studies on various adrenocortical models were done to establish novel therapeutic options. Results: Our human ACC dataset analyses showed high expression of HOXB9, and other HOX factors, are associated with poorer prognosis. Transgenic overexpression of Hoxb9 in the adrenal cortex of mice with activated Ctnnb1 led to larger adrenal tumours. This phenotype was preferentially observed in male mice and was characterised by more proliferating cells and an increase in the expression of cell cycle genes, including Ccne1. Adrenal tumour cells were found to be dependent on HOX function for survival and were sensitive to a specific peptide inhibitor. Conclusions: These studies show Hoxb9 can promote adrenal tumour progression in a sex-dependent manner and have identified HOX factors as potential drug targets, leading to novel therapeutic approaches in ACC.

Original languageEnglish
Pages (from-to)805-816
Number of pages12
JournalBritish Journal of Cancer
Issue number4
StatePublished - 16 Feb 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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