ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
RETRACTED: Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 69 papers, 1 of them a synthesis that pooled it.
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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
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- RHOA protein expression correlates with clinical features in gastric cancer: a systematic review and meta-analysis.BMC cancer · 2022Pooled it
- Early relapses after adjuvant chemotherapy suggests primary chemoresistance in diffuse gastric cancer.PloS one · 2017Trial
- Retraction Note: CDK5RAP3 as tumour suppressor negatively regulates self-renewal and invasion and is regulated by ERK1/2 signalling in human gastric cancer.British journal of cancer · 2026Article
- Resibufogenin and Oxaliplatin Synergistically Inhibit Diffuse Gastric Cancer by Inactivating the FAK/AKT/GSK3β/β-Catenin Signaling Pathway.Recent patents on anti-cancer drug discovery · 2026Article
- Diffuse Gastric Cancer: A Comprehensive Review of Molecular Features and Emerging Therapeutics.Targeted oncology · 2024Review
- Retraction: Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.Cancer cell international · 2024Review
- Research advances in the molecular classification of gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer.Cancer research and treatment · 2024Article
- Retraction Note: PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas.Oncogenesis · 2024Article
- Mutation characteristics and molecular evolution of ovarian metastasis from gastric cancer and potential biomarkers for paclitaxel treatment.Nature communications · 2024Article
- Retraction Note: 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 · 2024Article
- Opportunities in Cancer Therapies: Deciphering the Role of Cancer Stem Cells in Tumour Repopulation.International journal of molecular sciences · 2023Review
- Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice.Nature communications · 2023Article
- Review
- The complex of Fas-associated factor 1 with Hsp70 stabilizes the adherens junction integrity by suppressing RhoA activation.Journal of molecular cell biology · 2022Article
- Functional antagonism between CagA and DLC1 in gastric cancer.Cell death discovery · 2022Article
- EXOC4 Promotes Diffuse-Type Gastric Cancer Metastasis via Activating FAK Signal.Molecular cancer research : MCR · 2022Article
- Article
- Targeting HIF-1α/NOTCH1 pathway eliminates CD44Oncogene · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2024-10-15Duplication of/in Image · Euphemisms for Duplication · Investigation by Journal/Publisher ·
- Retracted
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe Lauren diffuse type of gastric adenocarcinoma (DGA), as opposed to the intestinal type (IGA), often harbors mutations in RHOA, but little is known about the role of RhoA in DGA. EXPERIMENTAL
designWe examined RhoA activity and RhoA pathway inhibition in DGA cell lines and in two mouse xenograft models. RhoA activity was also assessed in patient tumor samples.
resultsRhoA activity was higher in DGA compared with IGA cell lines and was further increased when grown as spheroids to enrich for cancer stem-like cells (CSCs) or when sorted using the gastric CSC marker CD44. RhoA shRNA or the RhoA inhibitor Rhosin decreased expression of the stem cell transcription factor, Sox2, and decreased spheroid formation by 78% to 81%. DGA spheroid cells had 3- to 5-fold greater migration and invasion than monolayer cells, and this activity was Rho-dependent. Diffuse GA spheroid cells were resistant in a cytotoxicity assay to 5-fluorouracil and cisplatin chemotherapy, and this resistance could be reversed with RhoA pathway inhibition. In two xenograft models, cisplatin inhibited tumor growth by 40% to 50%, RhoA inhibition by 32% to 60%, and the combination by 77% to 83%. In 288 patient tumors, increased RhoA activity correlated with worse overall survival in DGA patients (P = 0.017) but not in IGA patients (P = 0.612).
conclusionsRhoA signaling promotes CSC phenotypes in DGA cells. Increased RhoA activity is correlated with worse overall survival in DGA patients, and RhoA inhibition can reverse chemotherapy resistance in DGA CSC and in tumor xenografts. Thus, the RhoA pathway is a promising new target in DGA patients.
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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.