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SNAIL vs vitamin D receptor expression in colon cancer: therapeutics implications
1Instituto de Investigaciones Biomédicas 'Alberto Sols', Arturo Duperier 4, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, E-28029 Madrid, Spain.
Abstract:
Vitamin D analogues with reduced hypercalcemic activity are under clinical investigation for use against colon cancer and other neoplasias. However, only a subset of patients responds to this therapy, most probably due to loss of vitamin D receptor (VDR) expression during tumour progression. Recent data show that SNAIL transcription factor represses VDR expression, and thus abolishes the antiproliferative and prodifferentiation effects of VDR ligands in cultured cancer cells and their antitumour action in xenografted mice. Accordingly, upregulation of SNAIL in human colon tumours associates with downregulation of VDR. These findings suggest that SNAIL may be associated with loss of responsiveness to vitamin D analogues and may thus be used as an indicator of patients who are unlikely to respond to this therapy.
Insights
Vitamin D analogues show promise for colon cancer, but not all patients respond. The SNAIL factor may cause treatment resistance by reducing vitamin D receptor (VDR) expression, indicating non-responsive patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Vitamin D analogues are being investigated for colon cancer treatment due to their antiproliferative and prodifferentiation effects.
- Treatment response to vitamin D analogues varies significantly among patients, often linked to the loss of vitamin D receptor (VDR) expression during tumor progression.
Purpose of the Study:
- To investigate the role of the SNAIL transcription factor in regulating VDR expression in the context of colon cancer.
- To determine if SNAIL expression can serve as a predictive biomarker for patient response to vitamin D analogue therapy.
Main Methods:
- Examined the effect of SNAIL on VDR expression in cultured cancer cells.
- Assessed the antitumour activity of VDR ligands in xenograft mouse models.
- Correlated SNAIL and VDR expression levels in human colon tumor samples.
Main Results:
- SNAIL transcription factor was found to repress VDR expression, thereby inhibiting the antiproliferative and prodifferentiation effects of VDR ligands.
- SNAIL repressed VDR expression in cultured cancer cells and diminished the antitumour action of VDR ligands in vivo.
- Upregulation of SNAIL in human colon tumors was associated with a corresponding downregulation of VDR expression.
Conclusions:
- SNAIL transcription factor plays a critical role in VDR downregulation during colon tumor progression.
- SNAIL may be responsible for the loss of responsiveness to vitamin D analogue therapy in a subset of cancer patients.
- SNAIL expression could be a valuable biomarker to identify patients unlikely to benefit from vitamin D analogue treatment.
