ArticleOncotarget2017
mTOR signaling mediates resistance to tankyrase inhibitors in Wnt-driven colorectal cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Meta-analysis of integrated ChIP-seq and transcriptome data revealed genomic regions affected by estrogen receptor alpha in breast cancer.BMC medical genomics · 2023Pooled it
- MAGI3 deficiency unleashes β-catenin conformational change to drive metastatic progression and mTOR inhibitor resistance in ccRCC.Cell death & disease · 2026Article
- Understanding Tankyrase Inhibitors and Their Role in the Management of Different Cancer.Current cancer drug targets · 2025Review
- APC/PIK3CA mutations and β-catenin status predict tankyrase inhibitor sensitivity of patient-derived colorectal cancer cells.British journal of cancer · 2024Article
- Potential Role of Traditional Chinese Medicines by Wnt/β-Catenin Pathway Compared With Targeted Small Molecules in Colorectal Cancer Therapy.Frontiers in pharmacology · 2021Review
- Article
- Crossroads of telomere biology and anticancer drug discovery.Cancer science · 2020Review
- Are Wnt/β-Catenin and PI3K/AKT/mTORC1 Distinct Pathways in Colorectal Cancer?Cellular and molecular gastroenterology and hepatology · 2020Review
- Role of mTORC1 in intestinal epithelial repair and tumorigenesis.Cellular and molecular life sciences : CMLS · 2019Review
- Novel insight into the function of tankyrase.Oncology letters · 2018Review
- RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model.Cancer science · 2018Article
- Optimized base editors enable efficient editing in cells, organoids and mice.Nature biotechnology · 2018Article
- Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding.British journal of pharmacology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of Wnt/β-catenin signaling is essential for colorectal carcinogenesis. Tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, is a positive regulator of the Wnt/β-catenin signaling. Accordingly, tankyrase inhibitors are under preclinical development for colorectal cancer (CRC) therapy. However, Wnt-driven colorectal cancer cells are not equally sensitive to tankyrase inhibitors, and cellular factors that affect tankyrase inhibitor sensitivity remain elusive. Here, we established a tankyrase inhibitor-resistant cell line, 320-IWR, from Wnt/β-catenin-dependent CRC COLO-320DM cells. 320-IWR cells exhibited resistance to tankyrase inhibitors, IWR-1 and G007-LK, but remained sensitive to a PARP-1/2 inhibitor, olaparib, and several anti-CRC agents. In 320-IWR cells, nuclear localization of active β-catenin was decreased and expression of β-catenin target genes was constitutively repressed, suggesting that these cells repressed the Wnt/β-catenin signaling and were dependent on alternative proliferation pathways. 320-IWR cells exhibited upregulated mTOR signaling and were more sensitive to mTOR inhibition than the parental cells. Importantly, mTOR inhibition reversed resistance to tankyrase inhibitors and potentiated their anti-proliferative effects in 320-IWR cells as well as in CRC cell lines in which the mTOR pathway was intrinsically activated. These results indicate that mTOR signaling confers resistance to tankyrase inhibitors in CRC cells and suggest that the combination of tankyrase and mTOR inhibitors would be a useful therapeutic approach for a subset of CRCs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.