ArticleInternational journal of oncology2017
Isoform switch of CD44 induces different chemotactic and tumorigenic ability in gallbladder cancer.
Article in International journal of oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Prognostic value of CD44v9 expression in human cancers: A systematic review and meta-analysis.Medicine · 2020Pooled it
- Matrix Stiffness Directs Stemness Signatures in Breast Cancer.Advanced healthcare materials · 2026Article
- Sequential invasion assays identify carbonic anhydrase IX as a driver of invasiveness in epithelial triple-negative breast cancer cells.American journal of physiology. Cell physiology · 2026Article
- Decreased Endothelin-1 bioavailability impairs aggressiveness of gallbladder cancer cells.Biological research · 2025Article
- CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells.Stem cells (Dayton, Ohio) · 2025Review
- Review
- CD44 and its implication in neoplastic diseases.MedComm · 2024Review
- The Hyaluronan/CD44 Axis: A Double-Edged Sword in Cancer.International journal of molecular sciences · 2023Review
- RNA-binding proteins regulating the CD44 alternative splicing.Frontiers in molecular biosciences · 2023Review
- Tumor cell stemness in gastrointestinal cancer: regulation and targeted therapy.Frontiers in molecular biosciences · 2023Review
- Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors.Frontiers in oncology · 2023Article
- Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression.Cancer science · 2022Article
- Role of CD44 isoforms in epithelial-mesenchymal plasticity and metastasis.Clinical & experimental metastasis · 2022Review
- Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis.Oncology letters · 2022Review
- CD44: A Multifunctional Mediator of Cancer Progression.Biomolecules · 2021Review
- Functional analysis of CD44 variants and xCT in canine tumours.Veterinary medicine and science · 2021Article
- The role of alternative splicing in human cancer progression.American journal of cancer research · 2021Review
- Alternative splicing modulates cancer aggressiveness: role in EMT/metastasis and chemoresistance.Molecular biology reports · 2021Review
- The RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing.Nature communications · 2020Article
- CD44v9 Induces Stem Cell-Like Phenotypes in Human Cholangiocarcinoma.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gallbladder cancer (GBC) is one of the most unfavorable prognostic tumor, and immediate growth and distant metastasis are important factors associated with the poor prognosis of patients with this disease. Standard and variant isoforms of CD44 are associated with tumor growth, metastasis, and epithelial-mesenchymal transition (EMT), although their roles in GBC are unclear. We investigated the relationship between the CD44 isoforms with EMT, chemotaxis, and tumorigenicity. We analyzed CD44 expression in the GBC cell line NOZ and found that it comprises a major population that expressed CD44std+/CD44v9- (CD44s) and the minor population that expressed CD44std-/CD44v9+ (CD44v). CD44s cells exhibited increased chemotaxis and invasiveness compared with CD44v cells in in vitro cell migration and invasion assays. CD44s cells expressed higher and lower levels of mRNAs that encode vimentin and E-cadherin, respectively, compared with those of CD44v cells. CD44s cells expressed high levels of the transcription factors ZEB1 and ZEB2 that mediate EMT, and low levels of a splicing factor ESRP1 that controls the CD44 isoform switch. We performed in vivo mouse xenotransplantation analyses of CD44s and CD44v cells and found that CD44v cells exhibited relatively increased tumorigenicity. Immunohistochemical analysis of tissue microarrays revealed that high levels of CD44v9 and CD44std were associated with poorer prognosis. The expression of CD44std was also associated with poorly differentiated tumors and distant metastasis. In conclusion, CD44s was associated with a mesenchymal phenotype, increased chemotaxis and invasiveness, and decreased tumorigenicity. In contrast, CD44v cells exhibited an epithelial phenotype, decreased chemotaxis, decreased invasiveness, and increased tumorigenicity. These findings suggest that CD44v and CD44s cells play differently important roles in the progression and metastasis of GBC and the isoform switch triggers EMT.
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