Oncotarget | The transcription factor CUX1 negatively regulates invasion

Oncotarget Volume 11, Issue 9 reported CUX1 expression was increased in androgen-independent cells compared to androgen-sensitive cells.

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.

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.

Dr. Emma R. Dorris from the UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland said, "Prostate cancer is the second most common cancer in men, accounting for an estimated 14.5% of cancers diagnosed in men worldwide in 2018."

"Prostate cancer is the second most common cancer in men, accounting for an estimated 14.5% of cancers diagnosed in men worldwide in 2018."

- Dr. Emma R. Dorris, UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research

Prostate cancer is the fifth leading cause of death from cancer in men; 6.6% of the total men cancer deaths worldwide.

Studies in breast cancer have identified an association between elevated CUX1 expression and tumor progression and CUX1 expression was inversely correlated with relapse-free and overall survival in a small subset of breast cancer tissues.

CUX-1 has been shown to play a role in breast cancer progression and in drug resistance in gastric cancer but to date has a minimal functional association with prostate cancer.

Figure 1: CUX1 is differentially expressed in castrate resistant prostate cancer. (A) Gene expression of CUX1 using probes that detect transcript variants that produce full length (p200) CUX1 only (p = 0.003) or (B) full length p200CUX1 and alternatively spliced p75CUX1 transcript (p = 0.002) (C) Protein expression of CUX1 isoforms in whole cell line lysates (D) Proportion of p110/p200 CUX1 isoforms (densitometry n = 3 independent experiments, p = 0.045).

CUX1 also has distinct splice variants; the p75CUX1 isoform of the transcription factor has been associated with breast cancer and myeloid leukemia.

The Dorris Research Team concluded in their Oncotarget Research Paper, "We have demonstrated that CUX1 is differentially expressed in androgen-sensitive and androgen-independent prostate cancer cells. Silencing CUX1 in these cell lines have different phenotypic effects. The observed differences arise from the interplay between androgen-responsive genes (MMP3 and Cathepsin L) and differential expression of the CUX1 isoforms. Thus, 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 castrate-resistant prostate cancer and maybe an avenue for future work."

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DOI - https://doi.org/10.18632/oncotarget.27494

Full text - https://www.oncotarget.com/article/27494/text/

Correspondence to - Emma R. Dorris - emma.dorris@ucd.ie

Keywords - castration-resistant prostatic cancer, neoplasm invasiveness, androgen-independent prostatic cancer, recurrence

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