ArticleSignal transduction and targeted therapy2020
VDR-SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment.
Article in Signal transduction and targeted therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- VDR Activation Suppresses Pancreatic Cancer Metastasis Through Inhibition of the ERK Signaling Pathway.Cancers · 2026Article
- Construction of a diagnostic model for colorectal cancer based on exosome-related genes: integration of immune cell differentials and molecular docking.Translational cancer research · 2026Article
- Lactylation of SLC26A3 in the acidic tumor microenvironment promotes malignant progression of colorectal carcinoma.Cell death & disease · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Vitamin D Receptor in Cancer: Biological Functions, Mechanistic Insights, and Clinical Relevance.Cancer management and research · 2026Review
- Acidosis and the role of nanotechnology in mitigating cancer progression.Oncology reviews · 2026Review
- Vitamin D as a central modulator of thyroid diseases: mechanisms and clinical implications.Frontiers in immunology · 2026Review
- The symbiotic axis between the acidic tumor microenvironment and cancer stem cells: a driver of malignancy and therapeutic resistance.Frontiers in oncology · 2026Review
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- VDR Decrease Enhances the Efficacy of 1,25-Dihydroxyvitamin D3 Inhibiting Gefitinib Resistance by Regulating EGFR/FASN Loop in NSCLC Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- Role of the SOX family in cancer immune evasion: Emerging player and promising therapeutic opportunities.Medicine · 2025Review
- Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function.Nature communications · 2025Article
- Biomimetic Nano-delivery of Small-Molecule Piceatannol Modulates Tumor Stemness and Suppresses Colorectal Cancer Metastasis via Hippo/YAP1/SOX9 Signaling.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- A DNA Nanomachine Modulates the Stemness-Associated Signaling Pathways for Overcoming Chemoresistance by Temporally Programming Drug Release.Research (Washington, D.C.) · 2025Article
- Integrative machine learning and bioinformatics analysis to identify cellular senescence-related genes and potential therapeutic targets in ulcerative colitis and colorectal cancer.Frontiers in bioinformatics · 2025Article
- Promising roles of vitamin D receptor and APRO family proteins for the development of cancer stem cells targeted malignant tumor therapy.Oncology research · 2025Review
- Energy metabolism and the intestinal barrier: implications for understanding and managing intestinal diseases.Frontiers in microbiology · 2025Review
- Key genes of vitamin D metabolism and their roles in the risk and prognosis of cancer.Frontiers in genetics · 2025Review
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The acidic tumor microenvironment provides an energy source driving malignant tumor progression. Adaptation of cells to an acidic environment leads to the emergence of cancer stem cells. The expression of the vitamin D receptor (VDR) is closely related to the initiation and development of colorectal carcinoma (CRC), but its regulatory mechanism in CRC stem cells is still unclear. Our study revealed that acidosis reduced VDR expression by downregulating peroxisome proliferator-activated receptor delta (PPARD) expression. Overexpression of VDR effectively suppressed the stemness and oxaliplatin resistance of cells in acidosis. The nuclear export signal in VDR was sensitive to acidosis, and VDR was exported from the nucleus. Chromatin immunoprecipitation (ChIP) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analyses showed that VDR transcriptionally repressed SRY-box 2 (SOX2) by binding to the vitamin D response elements in the promoter of SOX2, impairing tumor growth and drug resistance. We demonstrated that a change in the acidic microenvironment combined with overexpression of VDR substantially restricted the occurrence and development of CRC in vivo. These findings reveal a new mechanism by which acidosis could affect the stemness of CRC cells by regulating the expression of SOX2 and show that abnormal VDR expression leads to ineffective activation of vitamin D signaling, resulting in a lack of efficacy of vitamin D in antineoplastic process.
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