ArticleCancer discovery2021
Cancer Cells Retrace a Stepwise Differentiation Program during Malignant Progression.
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 48 citations in OpenAlex.
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- An Integrative RNA Spliceosomic Landscape of Pancreatic Neuroendocrine Tumors Identifies Clinically Relevant Molecular Subgroups.Endocrine pathology · 2026Article
- TGIF2-mediated HMGB3 overexpression promotes esophageal squamous cell carcinoma proliferation and metastasis through TLR3/TGF-β signaling.Genes & diseases · 2026Article
- Rethinking gastroenteropancreatic neuroendocrine neoplasms: A perspective on cellular origins, molecular mechanisms, and combination therapies.Journal of translational internal medicine · 2026Article
- Establishment of patient-derived xenografts for neuroendocrine tumors in the avian embryo model.Endocrine-related cancer · 2026Article
- Genome-wide screenings identify BAP1 as a synthetic-lethality target with CDK4/6 inhibitors.Science advances · 2026Article
- Novel concepts of cell-of origin in neuroendocrine neoplasms.Virchows Archiv : an international journal of pathology · 2026Review
- Review
- Overview of high mobility group box 3 (HMGB3] protein.Molecular genetics and genomics : MGG · 2025Review
- Basic science and translational implications of current knowledge on neuroendocrine tumors.The Journal of clinical investigation · 2025Review
- Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025Review
- A new effLuc/Kate dual reporter allele for tumor imaging in mice.Disease models & mechanisms · 2025Article
- Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.Aging cell · 2024Article
- Interdependency and differential expression of ERK1 and ERK2 in breast and melanoma cell lines.Journal of the Egyptian National Cancer Institute · 2024Article
- Combined deletion of MEN1, ATRX and PTEN triggers development of high-grade pancreatic neuroendocrine tumors in mice.Scientific reports · 2024Article
- Cancer Evolution: A Multifaceted Affair.Cancer discovery · 2024Article
- A SOX9-B7x axis safeguards dedifferentiated tumor cells from immune surveillance to drive breast cancer progression.Developmental cell · 2023Article
- Reactivation of embryonic genetic programs in tissue regeneration and disease.Nature genetics · 2023Review
- Data-driven structural analysis of small cell lung cancer transcription factor network suggests potential subtype regulators and transition pathways.NPJ systems biology and applications · 2023Article
- Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer.BMC genomics · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Pancreatic neuroendocrine tumors (PanNET) comprise two molecular subtypes, relatively benign islet tumors (IT) and invasive, metastasis-like primary (MLP) tumors. Until now, the origin of aggressive MLP tumors has been obscure. Herein, using multi-omics approaches, we revealed that MLP tumors arise from IT via dedifferentiation following a reverse trajectory along the developmental pathway of islet β cells, which results in the acquisition of a progenitor-like molecular phenotype. Functionally, the miR-181cd cluster induces the IT-to-MLP transition by suppressing expression of the Meis2 transcription factor, leading to upregulation of a developmental transcription factor, Hmgb3. Notably, the IT-to-MLP transition constitutes a distinct step of tumorigenesis and is separable from the classic proliferation-associated hallmark, temporally preceding accelerated proliferation of cancer cells. Furthermore, patients with PanNET with elevated HMGB3 expression and an MLP transcriptional signature are associated with higher-grade tumors and worse survival. Overall, our results unveil a new mechanism that modulates cancer cell plasticity to enable malignant progression. SIGNIFICANCE: Dedifferentiation has long been observed as a histopathologic characteristic of many cancers, albeit inseparable from concurrent increases in cell proliferation. Herein, we demonstrate that dedifferentiation is a mechanistically and temporally separable step in the multistage tumorigenesis of pancreatic islet cells, retracing the developmental lineage of islet β cells.
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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.