ArticleCell cycle (Georgetown, Tex.)2014
Inhibition of C-terminal binding protein attenuates transcription factor 4 signaling to selectively target colon cancer stem cells.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 75 citations in OpenAlex.
- Why is the tumor microenvironment disordered by NADH/NADRedox biology · 2026Review
- NAD(H)-dependent corepressor CTBP1 integrates metabolic signals to drive oncogenic programs.Frontiers in immunology · 2026Review
- Review
- Identification and characterization of a new potent inhibitor targeting CtBP1/BARS in melanoma cells.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Regulation of SUMOylation Targets Associated With Wnt/β-Catenin Pathway.Frontiers in oncology · 2022Review
- Retinoic Acid-Induced 2 (RAI2) Is a Novel Antagonist of Wnt/β-Catenin Signaling Pathway and Potential Biomarker of Chemosensitivity in Colorectal Cancer.Frontiers in oncology · 2022Article
- The transrepression and transactivation roles of CtBPs in the pathogenesis of different diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Endoplasmic reticulum stress regulates the intestinal stem cell state through CtBP2.Scientific reports · 2021Article
- Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease.Cancer research · 2020Review
- Inflammation and DNA methylation coregulate the CtBP-PCAF-c-MYC transcriptional complex to activate the expression of a long non-coding RNAInternational journal of biological sciences · 2020Article
- Transforming growth factor beta (TGF-β) is activated by the CtBP2-p300-AP1 transcriptional complex in chronic renal failure.International journal of biological sciences · 2020Article
- C-terminal binding proteins 1 and 2 in traumatic brain injury-induced inflammation and their inhibition as an approach for anti-inflammatory treatment.International journal of biological sciences · 2020Article
- An intestinal stem cell niche inOncotarget · 2018Article
- The intracellular NADH level regulates atrophic nonunion pathogenesis through the CtBP2-p300-Runx2 transcriptional complex.International journal of biological sciences · 2018Article
- HBV Upregulates CtBP2 Expression via the X Gene.BioMed research international · 2018Article
- Hilbert-Schmidt and Sobol sensitivity indices for static and time series Wnt signaling measurements in colorectal cancer - part A.BMC systems biology · 2017Article
- CtBP- an emerging oncogene and novel small molecule drug target: Advances in the understanding of its oncogenic action and identification of therapeutic inhibitors.Cancer biology & therapy · 2017Review
- The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target.Molecular cancer therapeutics · 2017Review
- Somatostatin signaling via SSTR1 contributes to the quiescence of colon cancer stem cells.BMC cancer · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Selective targeting of cancer stem cells (CSCs), implicated in tumor relapse, holds great promise in the treatment of colorectal cancer. Overexpression of C-terminal binding protein (CtBP), an NADH dependent transcriptional regulator, is often observed in colon cancer. Of note, TCF-4 signaling is also up-regulated in colonic CSCs. We hypothesized that CtBP, whose dehydrogenase activity is amenable to pharmacological inhibition by 4-methylthio-2-oxobutyric acid (MTOB), positively regulates TCF-4 signaling, leading to CSC growth and self-renewal. CSCs demonstrated significant upregulation of CtBP1 and CtBP2 levels (mRNA and protein) and activity partly due to increased NADH/NAD ratio, as well as increased TCF/LEF transcriptional activity, compared to respective controls. Depletion of CtBP2 inhibited, while its overexpression enhanced, CSC growth (1° spheroids) and self-renewal (2°/3° spheroids). Similarly, MTOB caused a robust inhibition of spheroid growth and self-renewal in a dose dependent manner. MTOB displayed significantly greater selectivity for growth inhibition in the spheroids, at least in part through induction of apoptosis, compared to monolayer controls. Moreover, MTOB inhibited basal as well as induced (by GSK-3β inhibitor) TCF/LEF activity while suppressing mRNA and protein levels of several β-catenin target genes (CD44, Snail, C-MYC and LGR5). Lastly, CtBP physically interacted with TCF-4, and this interaction was significantly inhibited in the presence of MTOB. The above findings point to a novel role of CtBPs in the promotion of CSC growth and self-renewal through direct regulation of TCF/LEF transcription. Moreover, small molecular inhibition of its function can selectively target CSCs, presenting a novel approach for treatment of colorectal cancer focused on targeting of 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.