ArticleCell stem cell2019
De Novo PITX1 Expression Controls Bi-Stable Transcriptional Circuits to Govern Self-Renewal and Differentiation in Squamous Cell Carcinoma.
Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 41 citations in OpenAlex.
- Lineage master regulator and cancer-selective partner transcription factors rewire 3D genome topology for tumor-specific gene control.Science advances · 2026Article
- Oncogenic Ras drives EED degradation and PRC2 dysfunction to promote aggressive squamous cell carcinoma.Nature communications · 2026Article
- Single cell multiomics unravel the transcription networks controlling the different EMT tumor states.Nature communications · 2026Article
- SOX2 confers tumour permissiveness in a specific skin progenitor population.Nature communications · 2026Article
- The transcription factor PITX1 cooperates with super-enhancers to regulate the expression of DUSP4 and inhibit pyroptosis in pulmonary artery smooth muscle cells.Respiratory research · 2025Article
- Molecular and cellular dynamics of squamous cell carcinomas across tissues.Genes & development · 2025Review
- PITX1 as a grading, prognostic and tumor-infiltrating immune cells marker for chondrosarcoma: a public database-based immunoassay and tissue sample analysis.Frontiers in oncology · 2025Article
- Reprogramming of epidermal keratinocytes by PITX1 transforms the cutaneous cellular landscape and promotes wound healing.JCI insight · 2024Article
- Context-dependent roles of mitochondrial LONP1 in orchestrating the balance between airway progenitor versus progeny cells.Cell stem cell · 2024Article
- DUSP1 and SOX2 expression determine squamous cell carcinoma of the salivary gland progression.Scientific reports · 2024Article
- Stem-cell states converge in multistage cutaneous squamous cell carcinoma development.Science (New York, N.Y.) · 2024Article
- Mammalian esophageal stratified tissue homeostasis is maintained distinctively by the epithelial pluripotent p63Cellular and molecular life sciences : CMLS · 2023Article
- An epigenetic switch controls an alternative NR2F2 isoform that unleashes a metastatic program in melanoma.Nature communications · 2023Article
- PITX1 plays essential functions in cancer.Frontiers in oncology · 2023Review
- Intrinsic Networks Regulating Tissue Repair: Comparative Studies of Oral and Skin Wound Healing.Cold Spring Harbor perspectives in biology · 2022Review
- Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas.Translational cancer research · 2022Article
- Airway basal cells show regionally distinct potential to undergo metaplastic differentiation.eLife · 2022Article
- The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas.Cancers · 2022Review
- Prognostic Ability of Enhancer RNAs in Metastasis of Non-Small Cell Lung Cancer.Molecules (Basel, Switzerland) · 2022Article
- Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas.Cells · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Basal tumor propagating cells (TPCs) control squamous cell carcinoma (SCC) growth by self-renewing and differentiating into supra-basal SCC cells, which lack proliferative potential. While transcription factors such as SOX2 and KLF4 can drive these behaviors, their molecular roles and regulatory interactions with each other have remained elusive. Here, we show that PITX1 is specifically expressed in TPCs, where it co-localizes with SOX2 and TRP63 and determines cell fate in mouse and human SCC. Combining gene targeting with chromatin immunoprecipitation sequencing (ChIP-seq) and transcriptomic analyses reveals that PITX1 cooperates with SOX2 and TRP63 to sustain an SCC-specific transcriptional feed-forward circuit that maintains TPC-renewal, while inhibiting KLF4 expression and preventing KLF4-dependent differentiation. Conversely, KLF4 represses PITX1, SOX2, and TRP63 expression to prevent TPC expansion. This bi-stable, multi-input network reveals a molecular framework that explains self-renewal, aberrant differentiation, and SCC growth in mice and humans, providing clues for developing differentiation-inducing therapeutic strategies.
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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.