ArticleNature communications2016
Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 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
63 citing papers in PubMed, 118 citations in OpenAlex.
- Addition of SHR-1701 to first-line capecitabine and oxaliplatin (XELOX) plus bevacizumab for unresectable metastatic colorectal cancer.Signal transduction and targeted therapy · 2024Trial
- Comprehensive molecular characterization of cutaneous squamous cell carcinoma reveals determinants of metastatic progression.medRxiv : the preprint server for health sciences · 2026Article
- CDKN2A, ITGA3, SMAD4 and SIRT7 gene expression in human cutaneous squamous cell carcinoma development and pre-clinical diagnosis.BMC cancer · 2026Article
- The dynamics of mutational selection in cutaneous squamous carcinogenesis.Communications biology · 2026Article
- SOX2 confers tumour permissiveness in a specific skin progenitor population.Nature communications · 2026Article
- Article
- Partial-EMT cell state correlates with single cell pattern of invasion in head and neck SCC keratinocytes.The Journal of pathology · 2025Article
- CXCL16 Producing Tumor Clones Are Shaping Immunosuppressive Microenvironment in Squamous Cell Carcinoma via CXCR6 Regulatory T Cell.Cancer medicine · 2025Article
- Long-Term Latency of Highly Mutated Cells in Normal Mouse Skin Is Reversed by Exposure to Tumor Promoters and Chronic Tissue Damage.Cancer discovery · 2025Article
- The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review.Cancers · 2024Review
- Contribution of Keratinocytes in Skin Cancer Initiation and Progression.International journal of molecular sciences · 2024Review
- Cutaneous Squamous Cell Carcinoma: An Updated Review.Cancers · 2024Review
- First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-β receptor I inhibitor, in patients with advanced solid tumors.BMC cancer · 2024Article
- Complex and variable regulation of ΔNp63 and TAp63 by TGFβ has implications for the dynamics of squamous cell epithelial to mesenchymal transition.Scientific reports · 2024Article
- Review
- Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial.The Lancet regional health. Western Pacific · 2023Article
- 5,10,15,20-Tetrakis(pentafluorophenyl)porphyrin as a Functional Platform for Peptide Stapling and Multicyclisation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression.Nature communications · 2023Article
- Advances in cutaneous squamous cell carcinoma.Nature reviews. Cancer · 2023Review
- Combined Kdm6a and Trp53 Deficiency Drives the Development of Squamous Cell Skin Cancer in Mice.The Journal of investigative dermatology · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 9 institutions in 5 countries.
Funding
Abstract
Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFβ Smad signalling, which is localized to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through Braf(V600E) or Kras(G12D) knockin) and TGFβ signalling ablation (through Tgfbr1 deletion) in LGR5(+ve) stem cells enables rapid cSCC development in the mouse. Mutation of Tp53 (which is commonly mutated in sporadic cSCC) coupled with Tgfbr1 deletion in LGR5(+ve) cells also results in cSCC development. These findings indicate that LGR5(+ve) stem cells may act as cells of origin for cSCC, and that RAS/RAF/MAPK pathway hyperactivation or Tp53 mutation, coupled with loss of TGFβ signalling, are driving events of skin tumorigenesis.
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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.