ArticleMolecular cancer2014
SMURF1 silencing diminishes a CD44-high cancer stem cell-like population in head and neck squamous cell carcinoma.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Hesperidin and Hesperetin: Epigenetic-Stemness Crosstalk, Antitumor Mechanisms, Preclinical Data and Translation Barriers.Biomolecules · 2026Review
- CAV2 Modulates Cetuximab Sensitivity in HNSCC via Ubiquitin-Mediated Disruption of the PACT-PKR Axis.Cancers · 2026Article
- PADI4 facilitates stem-like properties and cisplatin resistance through upregulating PRMT2/IDs family in oesophageal squamous cell carcinoma.Clinical and translational medicine · 2025Article
- Overexpression of miR‑424‑5p reduces cisplatin resistance by downregulating SMURF1 in gastric cancer.Oncology letters · 2025Article
- Expression of SMURF family in pancreatic cancer and its effect on cell proliferation and migration.Frontiers in oncology · 2025Article
- LncRNA AFAP1-AS1 Promotes Oral Squamous Cell Carcinoma Development by Ubiquitin-Mediated Proteolysis.International dental journal · 2024Article
- Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges.Biomedicines · 2024Review
- Onco-Ontogeny of Squamous Cell Cancer of the First Pharyngeal Arch Derivatives.International journal of molecular sciences · 2024Review
- Cancer stem cells of head and neck squamous cell carcinoma; distance towards clinical application; a systematic review of literature.American journal of cancer research · 2023Review
- Neuron-specific enolase promotes stem cell-like characteristics of small-cell lung cancer by downregulating NBL1 and activating the BMP2/Smad/ID1 pathway.Oncogenesis · 2022Article
- Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years.Frontiers in cell and developmental biology · 2022Review
- Autophagy regulates the cancer stem cell phenotype of head and neck squamous cell carcinoma through the noncanonical FOXO3/SOX2 axis.Oncogene · 2022Article
- Targeting Cancer Stem Cell Markers or Pathways: A Potential Therapeutic Strategy for Oral Cancer Treatment.International journal of stem cells · 2021Review
- SMURF1, a promoter of tumor cell progression?Cancer gene therapy · 2021Review
- E3 Ubiquitin Ligases: Key Regulators of TGFβ Signaling in Cancer Progression.International journal of molecular sciences · 2021Review
- Role of cancer stem cells in head-and-neck squamous cell carcinoma - A systematic review.Journal of carcinogenesis · 2021Review
- Article
- Oncogenic Smurf1 promotes PTEN wild-type glioblastoma growth by mediating PTEN ubiquitylation.Oncogene · 2020Article
- ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas.Cell death & disease · 2020Article
- Propranolol Sensitizes Vascular Sarcoma Cells to Doxorubicin by Altering Lysosomal Drug Sequestration and Drug Efflux.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBone morphogenetic protein (BMP) signaling is thought to play key roles in regulating the survival and maintenance of cancer stem cells (CSCs), which contribute to disease recurrences and treatment failures in many malignances, including head and neck squamous cell carcinoma (HNSCC). Intracellular BMP signaling is regulated by SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) during cellular development. However, little is known about the role or regulation of BMP signaling in HNSCC CSCs.
methodsTwo CSC-like populations, CD44(high)/BMI1(high) and CD44(high)/ALDH(high), were enriched from HNSCC cell lines and evaluated for the expression of SMURF1 by qRT-PCR, flow cytometry, and immunoblotting. The activation status of BMP signaling in these populations was determined by using immunoblotting to detect phosphorylated SMAD1/5/8 (pSMAD1/5/8) levels. Knockdown of SMURF1 transcripts by RNA interference was used to assess the role of SMURF1 in BMP signaling and CSC maintenance. Loss of CSC-like phenotypes following SMURF1 knockdown was determined by changes in CD44(high) levels, cellular differentiation, and reduction in colony formation.
resultsPopulations of enriched CSC-like cells displayed decreased levels of pSMAD1/5/8 and BMP signaling target gene ID1 while SMURF1, CD44, and BMI1 were highly expressed when compared to non-CSC populations. Stable knockdown of SMURF1 expression in CSC-like cells increased pSMAD1/5/8 protein levels, indicating the reactivation of BMP signaling pathways. Decreased expression of SMURF1 also promoted adipogenic differentiation and reduced colony formation in a three-dimensional culture assay, indicating loss of tumorigenic capacity. The role of SMURF1 and inhibition of BMP signaling in maintaining a CSC-like population was confirmed by the loss of a CD44(high) expressing subpopulation in SMURF1 knockdown cells.
conclusionsOur findings suggest that inhibition of BMP signaling potentiates the long-term survival of HNSCC CSCs, and that this inhibition is mediated by SMURF1. Targeting SMURF1 and restoring BMP signaling may offer a new therapeutic approach to promote differentiation and reduction of CSC populations leading to reduced drug resistance and disease recurrence.
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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 Socratic graph.