ArticleCell communication and signaling : CCS2019
Characterization of CD44 intracellular domain interaction with RUNX2 in PC3 human prostate cancer cells.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Tumor-enriched circRNA TAFCR1 drives cancer progression and metastasis by disrupting UBE1-dependent TRIM21-mediated CD44 ubiquitination.Biomarker research · 2026Article
- Increased CD44 Expression in Endothelial Cells Induced by Advanced Glycation End Products Leads to Insufficient Maturation of Angiogenesis.Journal of cellular and molecular medicine · 2026Article
- Identifying the therapeutic potential of niclosamide in overcoming IFN-gamma dependent cancer immune evasion in the tumor microenvironment.Frontiers in immunology · 2026Article
- Natural medicines target tumor vascular microenvironment to inhibit tumor.Genes & diseases · 2025Review
- Evaluation of the Relationship between CD44 Expression and Gleason Grade among Prostate Adenocarcinoma and Benign Prostatic Hyperplasia: A Cross-Sectional Study.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025Article
- CD44 and its implication in neoplastic diseases.MedComm · 2024Review
- RUNX transcription factors: biological functions and implications in cancer.Clinical and experimental medicine · 2024Review
- Systems biology approach to identify biomarkers and therapeutic targets for colorectal cancer.Biochemistry and biophysics reports · 2024Article
- Targeted Delivery of Geraniol via Hyaluronic Acid-Conjugation Enhances Its Anti-Tumor Activity Against Prostate Cancer.International journal of nanomedicine · 2024Article
- 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
- Review
- Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway.Marine drugs · 2023Article
- Article
- Article
- Role of RUNX2 in breast cancer development and drug resistance (Review).Oncology letters · 2023Review
- Genetic heterogeneity of liver cancer stem cells.Anatomy & cell biology · 2023Article
- Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma.World journal of gastroenterology · 2022Review
- Melanoma stimulates the proteolytic activity of HaCaT keratinocytes.Cell communication and signaling : CCS · 2022Article
- Impairing proliferation of glioblastoma multiforme with CD44+ selective conjugated polymer nanoparticles.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundExpression of CD44 receptor is associated with the onset of several tumors. The intracellular domain of CD44 (CD44-ICD) has been implicated as a co-transcription factor for RUNX2 in the regulation of expression of MMP-9 in breast carcinoma cells. Previous studies from our laboratory demonstrated the role of CD44 in migration and invasion of PC3 prostate cells through activation of MMP-9. CD44 signaling regulates the phosphorylation and hence the localization of RUNX2 in the nucleus. The role of CD44-ICD has not been studied in prostate cancer cells. This study aimed to explore the role of CD44-ICD and RUNX2 in the regulation of expression of metastasis-related genes.
methodsPC3 and PC3 cells overexpressing RUNX2 protein were analyzed for RUNX2/CD44-ICD interaction by immunoprecipitation, immunoblotting, and Immunofluorescence analyses. Wound healing and tumorsphere formation analyses were also done in these cells. The real-time PCR analysis was used to detect the expression levels of different genes.
resultsExpression of CD44 and RUNX2 was observed only in PC3 cells (androgen receptor positive) and not in LNCaP or PCa2b cells (androgen receptor negative). Therefore, CD44-ICD fragment (~ 15-16 kDa) was observed in PC3 cells. Moreover, localization of CD44-ICD was more in the nucleus than in the cytoplasm of PC3 cells. Inhibition of cleavage of CD44 with a γ-secretase inhibitor, DAPT reduced the formation of CD44-ICD; however, accumulation of CD44-external truncation fragments (~ 20 and ~ 25 kDa) was detected. RUNX2 and CD44-ICD interact in the nucleus of PC3 cells, and this interaction was more in PC3 cells transfected with RUNX2 cDNA. Overexpression of RUNX2 augments the expression of metastasis-related genes (e.g., MMP-9 and osteopontin) which resulted in increased migration and tumorsphere formation.
conclusionsWe have shown here a strong functional relationship between CD44-ICD and RUNX2 in PC3 cells. RUNX2 forms a complex with CD44-ICD as a co-transcriptional factor, and this complex formation not only activates the expression of metastasis-related genes but also contributes to migration and tumorsphere formation. Therefore, RUNX2 and CD44-ICD are potential targets for anti-cancer therapy, and attenuation of their interaction may validate the regulatory effects of these proteins on cancer migration and progression.
Indexed as
Identifiers
What OpenQuestion holds
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.