ArticleCellular and molecular life sciences : CMLS2021
TGF-β1 promotes epithelial-to-mesenchymal transition and stemness of prostate cancer cells by inducing PCBP1 degradation and alternative splicing of CD44.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 78 citations in OpenAlex.
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- PCBP1 orchestrates amino acid metabolism burst during the naïve-to-primed pluripotency transition.Stem cell reports · 2026Article
- A Gene Feature Based on Histone Modifications Can Predict the Prognosis of Prostate Cancer.Biomedicines · 2026Article
- Single-Cell Transcriptomics Reveals Biomarkers for NK Cell Dysfunction in Endometriosis-Associated Immune Dysregulation.Mediators of inflammation · 2026Article
- Possible Roles for Purinergic Receptor P2RX4 in Breast and Prostate Cancers.International journal of molecular sciences · 2025Review
- CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells.Stem cells (Dayton, Ohio) · 2025Review
- Therapeutic strategies to reverse cigarette smoke-induced ion channel and mucociliary dysfunction in COPD airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Article
- Transforming Growth Factor-β Modulates Cancer Stem Cell Traits on CD44 Subpopulations in Hepatocellular Carcinoma.Journal of cellular biochemistry · 2025Article
- Best evidence linking the extracellular factor TGF-β to cancer-associated alternative splicing programs.BBA advances · 2025Review
- CD44 Immunohistochemical Expression in Central and Peripheral Parts of Prostatic Adenocarcinoma: An Institutional Study.Medicina (Kaunas, Lithuania) · 2024Article
- Deciphering the Tumor Microenvironment in Prostate Cancer: A Focus on the Stromal Component.Cancers · 2024Review
- From Sea to Science: Coral Aquaculture for Sustainable Anticancer Drug Development.Marine drugs · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- CD44 and its implication in neoplastic diseases.MedComm · 2024Review
- Extracellular matrix marker LAMC2 targets ZEB1 to promote TNBC malignancy via up-regulating CD44/STAT3 signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Aberrant activation of TGF-β/ROCK1 enhances stemness during prostatic stromal hyperplasia.Cell communication and signaling : CCS · 2024Article
- CRISPR/Cas9-mediated silencing of CD44: unveiling the role of hyaluronic acid-mediated interactions in cancer drug resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
CD44 is a marker of cancer stem cell (CSC) in many types of tumors. Alternative splicing of its 20 exons generates various CD44 isoforms that have different tissue specific expression and functions, including the CD44 standard isoform (CD44s) encoded by the constant exons and the CD44 variant isoforms (CD44v) with variant exon insertions. Switching between the CD44v and CD44s isoforms plays pivotal roles in tumor progression. Here we reported a novel mechanism of CD44 alternative splicing induced by TGF-β1 and its connection to enhanced epithelial-to-mesenchymal transition (EMT) and stemness in human prostate cancer cells. TGF-β1 treatment increased the expression of CD44s and N-cadherin while decreased the expression of CD44v and E-cadherin in DU-145 prostate cancer cells. Other EMT markers and cancer stem cell markers were also upregulated after TGF-β1 treatment. RNAi knockdown of CD44 reversed the phenotype, which could be rescued by overexpressing CD44s but not CD44v, indicating the alternatively spliced isoform CD44s mediated the activity of TGF-β1 treatment. Mechanistically, TGF-β1 treatment induced the phosphorylation, poly-ubiquitination, and degradation of PCBP1, a well-characterized RNA binding protein known to regulate CD44 splicing. RNAi knockdown of PCBP1 was able to mimic TGF-β1 treatment to increase the expression of CD44s, as well as the EMT and cancer stem cell markers. In vitro and in vivo experiments were performed to show that CD44s promoted prostate cancer cell migration, invasion, and tumor initiation. Taken together, we defined a mechanism by which TGF-β1 induces CD44 alternative splicing and promotes prostate cancer progression.
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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.