ArticleOncotarget2015
Cleaved CD44 intracellular domain supports activation of stemness factors and promotes tumorigenesis of breast cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 100 citations in OpenAlex.
- TGF-β2 promotes autophagy-mediated resistance to doxorubicin in metastatic colon cancer cells via HMGB1.Medical oncology (Northwood, London, England) · 2026Article
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- Tumor-enriched circRNA TAFCR1 drives cancer progression and metastasis by disrupting UBE1-dependent TRIM21-mediated CD44 ubiquitination.Biomarker research · 2026Article
- HC-HA/PTX3 from amniotic membrane reprograms human corneal fibroblasts to neural crest progenitors by switching from canonical to noncanonical TGFβ signaling.Stem cell research & therapy · 2026Article
- The bibliometric and visualized analysis on cancer stem cells in the early 21st century.International journal of surgery (London, England) · 2026Review
- The Role of the Fox Gene in Breast Cancer Progression.International journal of molecular sciences · 2025Review
- Toward Characterizing Lymphatic Vasculature in the Mammary Gland During Normal Development and Tumor-Associated Remodeling.Journal of mammary gland biology and neoplasia · 2024Review
- From mitochondria to tumor suppression: ACAT1's crucial role in gastric cancer.Frontiers in immunology · 2024Article
- CD44 Intracellular Domain: A Long Tale of a Short Tail.Cancers · 2023Review
- A Narrative Review on CD44's Role in Glioblastoma Invasion, Proliferation, and Tumor Recurrence.Cancers · 2023Review
- CD44 connects autophagy decline and ageing in the vascular endothelium.Nature communications · 2023Article
- Effects of Hyaluronan on Breast Cancer Aggressiveness.Cancers · 2023Review
- The role of tumor microenvironment on cancer stem cell fate in solid tumors.Cell communication and signaling : CCS · 2023Review
- Tissue-specific cancer stem/progenitor cells: Therapeutic implications.World journal of stem cells · 2023Review
- CD44 in Bone Metastasis Development: A Key Player in the Fate Decisions of the Invading Cells?Clinical & experimental metastasis · 2023Review
- In silico designing and expression of novel recombinant construct containing the variable part of CD44 extracellular domain for prediagnostic breast cancer.Cancer reports (Hoboken, N.J.) · 2023Article
- Ethyl Acetate Extract ofACS omega · 2023Article
- The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.International journal of biological sciences · 2023Review
- A recombinant adenovirus vector containing theFrontiers in oncology · 2023Article
- Exploring cell surface markers and cell-cell interactions of human breast milk stem cells.Journal of public health research · 2023Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD44 plays a role in the progression of tumors and is expressed in cancer stem cells (CSCs). However, the mechanisms underlying the crosstalk of CD44 with stemness genes in CSC maintenance remains unclear. In this study, we demonstrated how the cleaved intracellular domain of CD44 (CD44ICD) activates stemness factors such as Nanog, Sox2 and Oct4, and contributes to the tumorigenesis of breast cancer. We have found that the overexpression of CD44ICD increased mammosphere formation in breast cancer cells. Treatment with a γ-secretase inhibitor (GSI), which blocks the cleavage of CD44ICD, interfered with mammosphere formation. Interestingly, CD44ICD decreased the expression levels and nuclear localization of stemness factors, but overexpression of CD44ICD reversed these effects. In addition, we showed that nuclear localization of CD44ICD is important for transcriptional activation of the stemness factors. Furthermore, CD44ICD-overexpressed cells exhibited strong tumorigenecity and greater metastatic potential than did the control cells or CD44-depleted cells in vivo in mice models. Taken together, it was supposed that CD44 promotes tumorigenesis through the interaction and nuclear-translocation of its intracellular domain and stemness factors. We suggest that the prevention of cleavage and nuclear-translocation of CD44ICD is a potential target in treating breast cancer.
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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.