ArticleOncotarget2015
Chronic chemotherapeutic stress promotes evolution of stemness and WNT/beta-catenin signaling in colorectal cancer cells: implications for clinical use of WNT-signaling inhibitors.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Targeting Wnt/β-Catenin Pathway by DNA Alkylating Pyrrole-Imidazole Polyamide in Colon Cancer.Cancer science · 2026Article
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- The therapeutic effect of traditional Chinese medicine on breast cancer through modulation of the Wnt/β-catenin signaling pathway.Frontiers in pharmacology · 2024Review
- Metformin activates Wnt/β-catenin for the treatment of diabetic osteoporosis.BMC endocrine disorders · 2022Article
- The C-Terminal Acidic Tail Modulates the Anticancer Properties of HMGB1.International journal of molecular sciences · 2022Article
- Wnt/β-Catenin Inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer.Frontiers in oncology · 2022Article
- Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.Cancer communications (London, England) · 2021Review
- Osteopontin as a Regulator of Colorectal Cancer Progression and Its Clinical Applications.Cancers · 2021Review
- Combating Drug Resistance in Colorectal Cancer Using Herbal Medicines.Chinese journal of integrative medicine · 2021Review
- Review
- Secondary Metabolites from the Culture of the Marine-derived FungusMarine drugs · 2020Article
- Mechanisms behind prometastatic changes induced by neoadjuvant chemotherapy in the breast cancer microenvironment.Breast cancer (Dove Medical Press) · 2019Article
- Article
- Review
- WNT Signaling in Cardiac and Vascular Disease.Pharmacological reviews · 2018Review
- Bufalin reverses acquired drug resistance by inhibiting stemness in colorectal cancer cells.Oncology reports · 2017Article
- WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity.Scientific reports · 2017Article
- Wnt/beta-catenin pathway: modulating anticancer immune response.Journal of hematology & oncology · 2017Review
- Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most solid tumors contain a subfraction of cells with stem/progenitor cell features. Stem cells are naturally chemoresistant suggesting that chronic chemotherapeutic stress may select for cells with increased "stemness". We carried out a comprehensive molecular and functional analysis of six independently selected colorectal cancer (CRC) cell lines with acquired resistance to three different chemotherapeutic agents derived from two distinct parental cell lines. Chronic drug exposure resulted in complex alterations of stem cell markers that could be classified into three categories: 1) one cell line, HT-29/5-FU, showed increased "stemness" and WNT-signaling, 2) three cell lines showed decreased expression of stem cell markers, decreased aldehyde dehydrogenase activity, attenuated WNT-signaling and lost the capacity to form colonospheres and 3) two cell lines displayed prominent expression of ABC transporters with a heterogeneous response for stem cell markers. While WNT-signaling could be attenuated in the HT-29/5-FU cells by the WNT-signaling inhibitors ICG-001 and PKF-118, this was not accompanied by any selective growth inhibitory effect suggesting that the cytotoxic activity of these compounds is not directly linked to WNT-signaling inhibition. We conclude that classical WNT-signaling inhibitors have toxic off-target activities that need to be addressed for clinical development.
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