ArticleProceedings of the National Academy of Sciences of the United States of America2014
Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-β-SMAD3 pathway in non-small cell lung adenocarcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- E2F4 Program Is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer.Molecular cancer research : MCR · 2015Pooled it
- Synthesis and Development of Novel Small-Molecule MEIS2 Inhibitors That Induce Cell Death in Breast Cancer Cells by Targeting the Homeobox Domain.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Pirfenidone Suppresses Liver Fibrosis Through Inhibition of TGF-β-Associated Lipid Metabolic Remodeling in Hepatic Stellate Cells.International journal of molecular sciences · 2026Article
- ANKRD49 promotes the epithelial-mesenchymal transition of non-small cell lung cancer via the PKNOX1/TGF-β1/SMAD axis.Cancer cell international · 2026Article
- Identification of key biomarkers and potential therapeutic drugs in nasopharyngeal carcinoma based on comprehensive bioinformatics analysis.Discover oncology · 2025Article
- TCF7 functions as a prognostic biomarker in bladder cancer by strengthening EMT and stemness associated with TGF-β/SMAD3 signaling.Molecular and cellular biochemistry · 2025Article
- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Systematic pan-cancer analysis identifies PKNOX1 as a potential prognostic and immunological biomarker and its functional validation.Frontiers in immunology · 2025Article
- Conservation ofCells · 2024Article
- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia.Nature communications · 2023Article
- The origin of brain malignancies at the blood-brain barrier.Cellular and molecular life sciences : CMLS · 2023Review
- PCB: A pseudotemporal causality-based Bayesian approach to identify EMT-associated regulatory relationships of AS events and RBPs during breast cancer progression.PLoS computational biology · 2023Article
- PTBP3 mediates TGF-β-induced EMT and metastasis of lung adenocarcinoma.Cell cycle (Georgetown, Tex.) · 2022Article
- The transcription factor PREP1(PKNOX1) regulates nuclear stiffness, the expression of LINC complex proteins and mechanotransduction.Communications biology · 2022Article
- MicroRNA-141-3p inhibits the progression of oral squamous cell carcinoma via targeting PBX1 through the JAK2/STAT3 pathway.Experimental and therapeutic medicine · 2022Article
- PBX1: a key character of the hallmarks of cancer.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Development of small molecule inhibitors targeting PBX1 transcription signaling as a novel cancer therapeutic strategy.iScience · 2021Article
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5 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Pre-B-cell leukemia homeobox (Pbx)-regulating protein-1 (Prep1) is a ubiquitous homeoprotein involved in early development, genomic stability, insulin sensitivity, and hematopoiesis. Previously we have shown that Prep1 is a haploinsufficient tumor suppressor that inhibits neoplastic transformation by competing with myeloid ecotropic integration site 1 for binding to the common heterodimeric partner Pbx1. Epithelial-mesenchymal transition (EMT) is controlled by complex networks of proinvasive transcription factors responsive to paracrine factors such as TGF-β. Here we show that, in addition to inhibiting primary tumor growth, PREP1 is a novel EMT inducer and prometastatic transcription factor. In human non-small cell lung cancer (NSCLC) cells, PREP1 overexpression is sufficient to trigger EMT, whereas PREP1 down-regulation inhibits the induction of EMT in response to TGF-β. PREP1 modulates the cellular sensitivity to TGF-β by inducing the small mothers against decapentaplegic homolog 3 (SMAD3) nuclear translocation through mechanisms dependent, at least in part, on PREP1-mediated transactivation of a regulatory element in the SMAD3 first intron. Along with the stabilization and accumulation of PBX1, PREP1 induces the expression of multiple activator protein 1 components including the proinvasive Fos-related antigen 1 (FRA-1) oncoprotein. Both FRA-1 and PBX1 are required for the mesenchymal changes triggered by PREP1 in lung tumor cells. Finally, we show that the PREP1-induced mesenchymal transformation correlates with significantly increased lung colonization by cells overexpressing PREP1. Accordingly, we have detected PREP1 accumulation in a large number of human brain metastases of various solid tumors, including NSCLC. These findings point to a novel role of the PREP1 homeoprotein in the control of the TGF-β pathway, EMT, and metastasis in NSCLC.
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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.