HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours.
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Embargo End Date
ICR Authors
Authors
Francis, JC
Gardiner, JR
Renaud, Y
Chauhan, R
Weinstein, Y
Gomez-Sanchez, C
Lefrançois-Martinez, A-M
Bertherat, J
Val, P
Swain, A
Gardiner, JR
Renaud, Y
Chauhan, R
Weinstein, Y
Gomez-Sanchez, C
Lefrançois-Martinez, A-M
Bertherat, J
Val, P
Swain, A
Document Type
Journal Article
Date
2021-02-16
Date Accepted
2020-10-29
Abstract
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.
Citation
British journal of cancer, 2020
Source Title
Publisher
Springer Science and Business Media LLC
ISSN
0007-0920
eISSN
1532-1827
Collections
Research Team
Development & Cancer
Development & Cancer
Development & Cancer