ArticleOncotarget2018
The anti-cancer effect of retinoic acid signaling in CRC occurs via decreased growth of ALDH+ colon cancer stem cells and increased differentiation of stem cells.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 45 citations in OpenAlex.
- Inhibition of WNT signaling sensitizes CRC cells to anti-tumor effects of retinoids: basis for new drug combinations in oncology.Cancer biology & therapy · 2026Article
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Imbalance in WNT: retinoic acid signaling dysregulates HOX gene expression: implications for cancer stem cell heterogeneity and CRC patient survival.Stem cells translational medicine · 2026Article
- Pleiotropic effects of all-trans retinoic acid in attenuating the hallmarks of colorectal cancer- challenges and scope of differentiation therapy.Cancer gene therapy · 2026Review
- NAD(H)-dependent corepressor CTBP1 integrates metabolic signals to drive oncogenic programs.Frontiers in immunology · 2026Review
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Dynamic Organization of Cells in Colonic Epithelium is Encoded by Five Biological Rules.Biology of the cell · 2025Article
- Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-β1 signaling mechanism.Journal of experimental & clinical cancer research : CR · 2025Article
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Metabolic Targets in CRC: The Emerging Role of Cytochrome P450 Inhibitors.Current pharmaceutical design · 2025Review
- The Significance of Aldehyde Dehydrogenase 1 in Cancers.International journal of molecular sciences · 2024Review
- Delineating the role of nuclear receptors in colorectal cancer, a focused review.Discover oncology · 2024Review
- Article
- Inactivation of interleukin-30 in colon cancer stem cells via CRISPR/Cas9 genome editing inhibits their oncogenicity and improves host survival.Journal for immunotherapy of cancer · 2023Article
- Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer.Journal of stem cell research & therapy · 2023Article
- HOXA9 Overexpression Contributes to Stem Cell Overpopulation That Drives Development and Growth of Colorectal Cancer.International journal of molecular sciences · 2022Article
- Article
- Aldehyde Dehydrogenases Expression in Corneal Epithelial Cells with Limbal Stem Cell Deficiency.International journal of molecular sciences · 2022Article
- Involvement of hedgehog signaling in all-trans retinoic acid-mediated suppression of colon cancer.American journal of translational research · 2022Article
- Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer.iScience · 2021Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTumorigenesis is driven by stem cell (SC) overpopulation. Because ALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA) signaling, we studied RA signaling in normal and malignant colonic SCs. HYPOTHESIS: RA signaling regulates growth and differentiation of ALDH+ colonic SCs; dysregulation of RA signaling contributes to SC overpopulation and colorectal cancer (CRC) development.
methodsWe analyzed normal and malignant colonic tissues and CRC cell lines to see if retinoid receptors (RXR & RAR) are exclusively expressed in ALDH+ SCs, and if RA signaling changes during CRC development. We determined whether RA signaling regulates cancer SC (CSC) proliferation, differentiation, sphere formation, and population size.
resultsRXR & RAR were expressed in ALDH+ colonic SCs, but not in MCM2+ proliferative cells. Western blotting/immunostaining of CRCs revealed that RA signaling components become overexpressed in parallel with ALDH overexpression, which coincides with the known overpopulation of ALDH+ SCs that occurs during, and drives, CRC development. Treatment of SCs with all-trans retinoic acid (ATRA) decreased proliferation, sphere formation and ALDH+ SC population size, and induced differentiation along the neuroendocrine cell (NEC) lineage.
conclusionsRetinoid signaling, by regulating ALDH+ colonic CSCs, decreases SC proliferation, sphere formation, and population size, and increases SC differentiation to NECs. Dysregulation of RA signaling in colonic SCs likely contributes to overpopulation of ALDH+ SCs and CRC growth. IMPLICATIONS: That retinoid receptors RXR and RAR are selectively expressed in ALDH+ SCs indicates RA signaling mainly occurs via ALDH+ SCs, which provides a mechanism to selectively target CSCs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.