ArticleOncogene2016
SFRP2 augments WNT16B signaling to promote therapeutic resistance in the damaged tumor microenvironment.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 77 papers.
What it found
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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.
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Who cites it
77 citing papers in PubMed, 118 citations in OpenAlex.
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- Tumor budding and poorly differentiated clusters as a biological continuum in colorectal cancer invasion and prognosis.Scientific reports · 2025Article
- Targeting Senescence with Apigenin Improves Chemotherapeutic Efficacy and Ameliorates Age-Related Conditions in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Investigating the Role ofCancers · 2024Article
- Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy.Aging cell · 2024Article
- SFRP2 modulates functional phenotype transition and energy metabolism of macrophages during diabetic wound healing.Frontiers in immunology · 2024Article
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- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- Engineered bone marrow as a clinically relevant ex vivo model for primary bone cancer research and drug screening.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis.Scientific reports · 2023Article
- Cellular Transcriptomics of Carboplatin Resistance in a Metastatic Canine Osteosarcoma Cell Line.Genes · 2023Article
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- Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence.Frontiers in oncology · 2023Article
- High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data.Frontiers in physiology · 2023Article
- Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer.Frontiers in oncology · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2024-11-19Concerns/Issues about Data · Duplication of/in Image · Investigation by Journal/Publisher · Lack of IRB/IACUC Approval and/or Compliance · Objections by Author(s) · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most tumors initially respond to cytotoxic treatments, but acquired resistance often follows. The tumor microenvironment (TME) is a major barrier to clinical success by compromising therapeutic efficacy, and pathological relevance of multiple soluble factors released by a therapeutically remodeled TME remains largely unexplored. Here we show that the secreted frizzled-related protein 2 (SFRP2), a Wnt pathway modulator, is produced by human primary fibroblasts after genotoxic treatments. SFRP2 induction is remarkable in tumor stroma, with transcription mainly modulated by the nuclear factor-κB (NF-κB) complex, a property shared by several effectors of the DNA damage secretory program. Instead of directly altering canonical Wnt signaling, SFRP2 augments β-catenin activities initiated by WNT16B, another soluble factor from DNA-damaged stroma. WNT16B recognizes cancer cell surface receptors including frizzled (FZD) 3/4/6, a process enhanced by SFRP2, coordinated by the co-receptor LRP6 but subject to abrogation by DKK1. Importantly, we found WNT16B plays a central role in promoting advanced malignancies particularly acquired resistance by counteracting cell death, an effect that can be minimized by a neutralizing antibody co-administered with classical chemotherapy. Furthermore, DNA damage-triggered expression of WNT16B is systemic, imaged by significant induction among diverse solid organs and circulation in peripheral blood, thereby holding promise as not only a TME-derived anticancer target but also a novel biomarker for clinical evaluation of treatment efficacy. Overall, our study substantiates the biological complexity and pathological implication of a therapy-activated TME, and provides the proof of principle of co-targeting tumor and the TME to prevent acquired resistance, with the aim of improving intervention outcome in an era of precision medicine.
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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.