Oncotarget

Research Papers:

The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer

Emma R. Dorris _, Amanda O’Neill, Ann Treacy, Helmut Klocker, Omri Teltsh, Elaine Kay and R. William Watson

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Oncotarget. 2020; 11:846-857. https://doi.org/10.18632/oncotarget.27494

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Abstract

Emma R. Dorris1, Amanda O’Neill1, Ann Treacy2, Helmut Klocker3, Omri Teltsh1, Elaine Kay4 and R. William Watson1

1 UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland

2 Pathology Department, Mater Private Hospital, Dublin, Ireland

3 Department of Urology, Medical University of Innsbruck, Innsbruck, Austria

4 Department of Pathology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland

Correspondence to:

Emma R. Dorris,email: emma.dorris@ucd.ie

Keywords: castration-resistant prostatic cancer; neoplasm invasiveness; androgen-independent prostatic cancer; recurrence

Received: August 06, 2019     Accepted: January 29, 2020     Published: March 03, 2020

ABSTRACT

Metastatic prostate cancer is treated with androgen ablation therapy but progress to castrate resistant prostate cancer (CRPC). This study aimed to investigate the role of CUX1 in CRPC using clinical samples and in vitro models. CUX1 expression was increased in androgen-independent cells compared to androgen-sensitive cells. The multi-isoform nature of CUX1 makes it difficult to assay in tissue microarrays as there is no epitope able to distinguish the many isoforms for immunohistochemistry. Using surrogate markers, we found no differential expression between castrate resistant and local hormone naïve tissue. However, differences have been demonstrated at the transcript level. In androgen-sensitive cells, migration, but not invasion, increased following CUX1 knockdown. Conversely, in androgen-independent cells, invasion was increased. This observed difference in invasion capacity is not E-cadherin mediated, as CUX1 knockdown increases the expression of E-cadherin in both cell lines with no inter-cell line difference. Cells expressed different ratios of p110/p200 isoforms depending on androgen status and cathepsin L was only detectable in androgen-sensitive cells. MMP3 is upregulated in the androgen-independent cells. Rather than a simple presence or absence of CUX1, the relative balance of CUX1 isoforms and their interplay may be a significant factor in the functional role of CUX1 in CRPC.


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