ArticleOncotarget2016
A reciprocal regulatory circuit between CD44 and FGFR2 via c-myc controls gastric cancer cell growth.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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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.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- The Role of FGFR2 as a Novel Biomarker for Treatment of Gastric Cancer-A Literature Review.Medicina (Kaunas, Lithuania) · 2025Review
- Article
- Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells.The Journal of clinical investigation · 2025Article
- Unveiling the hidden dance: SPP1 + macrophages identified in ulcerative colitis reveal crosstalk with CHI3L1 + fibroblasts.Journal of translational medicine · 2025Article
- The FGF/FGFR/c-Myc axis as a promising therapeutic target in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2024Review
- Article
- Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.Nature biomedical engineering · 2023Article
- Review
- Review
- Review
- CD44 promotes angiogenesis in myocardial infarction through regulating plasma exosome uptake and further enhancing FGFR2 signaling transduction.Molecular medicine (Cambridge, Mass.) · 2022Article
- AZD4547 targets the FGFR/Akt/SOX2 axis to overcome paclitaxel resistance in head and neck cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Stem cell-like circulating tumor cells indicate poor prognosis in gastric cancer.Archives of medical science : AMS · 2022Article
- CD44: A Multifunctional Mediator of Cancer Progression.Biomolecules · 2021Review
- Article
- The beginning of the era of precision medicine for gastric cancer with fibroblast growth factor receptor 2 aberration.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Review
- Comprehensive Analysis of Fibroblast Growth Factor Receptor (FGFR) Family Genes in Breast Cancer by Integrating Online Databases and Bioinformatics.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- The biology and role of CD44 in cancer progression: therapeutic implications.Journal of hematology & oncology · 2018Review
- Regulation of Gastric Lgr5+ve Cell Homeostasis by Bone Morphogenetic Protein (BMP) Signaling and Inflammatory Stimuli.Cellular and molecular gastroenterology and hepatology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite their suggested importance, the mechanistic roles of FGFR2 and gastric cancer stem cell (GCSC) marker CD44 remain unclear. We investigated cross talk between CD44 and FGFR2. FGFR2 and CD44 positively regulate each other's expression. While FGFR2 suppresses c-Myc transcription, CD44 activates it. c-Myc in turn augments FGFR2 transcription. CD44 knockdown (KD) depleted FGFR2 and other GCSC markers, decreased c-Myc and Sox2 expression, and suppressed tumor growth, whereas CD44 activation led to FGFR2 induction. FGFR2 KD decreased most GCSC marker expression, including CD44, but increased c-Myc and Sox2 expression and attenuated tumor growth. FGFR2 kinase inhibitor and FGFR2 neutralizing antibody decreased the CD44+/hi GCSC fraction. Conversely, FGFR2 overexpression increased CD44 and accelerated tumor growth in mice. FGFR2 was co-expressed and colocalized diffusively with CD44, EpCAM, and LGR5. In contrast, phospho-FGFR2 colocalized densely with CD44, forming an aggregated signaling complex that was prevented by FGFR2 inhibition. The c-Myc KD depleted FGFR2 but not CD44. Similarly to CD44+/hi phenotypes, sorted FGFR+/hi cells had larger volumes, formed more tumor spheres, grew faster in vivo with bigger tumor mass, and expressed more CD44, EpCAM, and HER2. These findings suggest that FGFR2+/hi cells have stemness properties. Moreover, in situ FGFR2 expression in patient-derived gastric cancer tissue correlated with tumorigenic potential in a xenograft model. In conclusion, CD44 and FGFR2 maintain stemness in gastric cancer by differentially regulating c-Myc transcription.
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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.