ArticleEBioMedicine2019
Rab8 GTPase regulates Klotho-mediated inhibition of cell growth and progression by directly modulating its surface expression in human non-small cell lung cancer.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Suyin Detoxification Prescription Regulates the Klotho and ERK/NF-κB Signaling Pathways to Alleviate Renal Injury.Cell biochemistry and biophysics · 2025Article
- Construction of a prognostic model for lung adenocarcinoma based on necroptosis genes and its exploration of the potential for tumor immunotherapy.Translational cancer research · 2025Article
- Klotho-beta attenuates Rab8a-mediated exosome regulation and promotes prostate cancer progression.Oncogene · 2023Article
- [Research Progress of Klotho in Lung Neoplasms].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Transcription Activation of Rab8A by PEA3 Augments Progression of Esophagus Cancer by Activating the Wnt/Disease markers · 2023Article
- SHANK1 facilitates non-small cell lung cancer processes through modulating the ubiquitination of Klotho by interacting with MDM2.Cell death & disease · 2022Article
- CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases.Frontiers in genetics · 2022Review
- Development of a Bile Acid-Related Gene Signature for Predicting Survival in Patients with Hepatocellular Carcinoma.Computational and mathematical methods in medicine · 2022Article
- Exosomal Components and Modulators in Colorectal Cancer: Novel Diagnosis and Prognosis Biomarkers.Biomedicines · 2021Review
- A methylation-based nomogram for predicting survival in patients with lung adenocarcinoma.BMC cancer · 2021Article
- Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer.Frontiers in cell and developmental biology · 2020Review
- Circular RNA ITCH suppresses metastasis of gastric cancer via regulating miR-199a-5p/Klotho axis.Cell cycle (Georgetown, Tex.)Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe klotho (KL) gene is an anti-aging gene that has recently been shown to also function as a general tumor suppressor. However, there is currently only limited information regarding the potential molecular signals for regulation of Klotho without identifying precise molecular mechanisms or interactions.
methodsWe performed a mass spectrometry (MS) assay to screen candidate proteins complexed with Klotho derived from immunoprecipitation in human non-small cell lung cancer (NSCLC) cells, and identified Rab8 to be the protein that most prominently interacts with Klotho. We further investigated whether Rab8 can regulate trafficking of Klotho and which process it would modulate using surface biotinylation assay, immunofluorescence and fluorescence ratio microscopy. Furthermore, we explored whether Rab8 is involved in Klotho-mediated function in NSCLC, and verified the results which we found in vivo using xenograft mouse model.
findingsWe report discovery of Rab8 as a Klotho-interacting protein that acts as a critical modulator of Klotho surface expression in human NSCLC. In particular, we report that Rab8 is co-localized and associated with Klotho, and Klotho trafficking is regulated by Rab8. Moreover, we found that Rab8 modulates surface levels of Klotho via a post-biosynthetic pathway, as opposed to an endocytic pathway. Furthermore, we demonstrate that Rab8 is involved in Klotho-mediated regulation of cell proliferation, migration, invasiveness, epithelial-mesenchymal transition (EMT), and Wnt-β-catenin signaling in NSCLC. Additionally, Rab8 overexpression was also found to increase Klotho-mediated inhibition of NSCLC tumorigenesis in vivo.
interpretationOverall, our findings suggest that Rab8 GTPase can regulate Klotho-mediated inhibition of Wnt signaling activity by modulating translocation of Klotho onto the cell surface, which in turn affects Klotho-mediated inhibition of cell proliferation, migration and invasiveness in NSCLC. These results have important implications for the development of new therapeutic targets, Klotho-related research in the context of NSCLC as well as other areas, and provide a working model for Rab8 function in the context of cancer and cancer biology.
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