ArticleThe Journal of biological chemistry2012
The plasma membrane sialidase NEU3 regulates the malignancy of renal carcinoma cells by controlling β1 integrin internalization and recycling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 63 citations in OpenAlex.
- Modulating the sialic acid content of endothelial cells affects their adhesion and barrier permeability.Scientific reports · 2026Article
- Decoding sialidase: physiological roles, pathological pathways, and clinical opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Sialidases as Potential Therapeutic Targets for Treatment of a Number of Human Diseases.International journal of molecular sciences · 2025Review
- Single-cell transcriptomics identify a chemotherapy-resistance related cluster overexpressed CLIC3 in ovarian cancer.Discover oncology · 2025Article
- The Ying and Yang of Ganglioside Function in Cancer.Cancers · 2023Review
- Characterization of Lipid Alterations by OncogenicOmics : a journal of integrative biology · 2023Article
- Lipids as Targets for Renal Cell Carcinoma Therapy.International journal of molecular sciences · 2023Review
- Sialyltransferases and Neuraminidases: Potential Targets for Cancer Treatment.Diseases (Basel, Switzerland) · 2022Review
- Review
- Sphingolipids and Lymphomas: A Double-Edged Sword.Cancers · 2022Review
- Role of glycosyltransferases in carcinogenesis; growth factor signaling and EMT/MET programs.Glycoconjugate journal · 2022Review
- Inhibitors of Human Neuraminidase Enzymes Block TransmigrationFrontiers in molecular biosciences · 2022Article
- Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance.Molecular oncology · 2021Review
- Gangliosides as Signaling Regulators in Cancer.International journal of molecular sciences · 2021Review
- Rab GTPases: Central Coordinators of Membrane Trafficking in Cancer.Frontiers in cell and developmental biology · 2021Review
- Elucidating the expression and function of Numbl during cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma (MM).BMC cancer · 2019Article
- Ganglioside GM2, highly expressed in the MIA PaCa-2 pancreatic ductal adenocarcinoma cell line, is correlated with growth, invasion, and advanced stage.Scientific reports · 2019Article
- Neuraminidase-3 Is a Negative Regulator of LFA-1 Adhesion.Frontiers in chemistry · 2019Article
- Identification of potential pathogenic biomarkers in clear cell renal cell carcinoma.Oncology letters · 2018Article
- Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin.Experimental & molecular medicine · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human plasma membrane sialidase NEU3 is a key enzyme in the catabolism of membrane gangliosides, is crucial in the regulation of cell surface processes, and has been demonstrated to be significantly up-regulated in renal cell carcinomas (RCCs). In this report, we show that NEU3 regulates β1 integrin trafficking in RCC cells by controlling β1 integrin recycling to the plasma membrane and controlling activation of the epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK)/protein kinase B (AKT) signaling. NEU3 silencing in RCC cells increased the membrane ganglioside content, in particular the GD1a content, and changed the expression of key regulators of the integrin recycling pathway. In addition, NEU3 silencing up-regulated the Ras-related protein RAB25, which directs internalized integrins to lysosomes, and down-regulated the chloride intracellular channel protein 3 (CLIC3), which induces the recycling of internalized integrins to the plasma membrane. In this manner, NEU3 silencing enhanced the caveolar endocytosis of β1 integrin, blocked its recycling and reduced its levels at the plasma membrane, and, consequently, inhibited EGFR and FAK/AKT. These events had the following effects on the behavior of RCC cells: they (a) decreased drug resistance mediated by the block of autophagy and the induction of apoptosis; (b) decreased metastatic potential mediated by down-regulation of the metalloproteinases MMP1 and MMP7; and (c) decreased adhesion to collagen and fibronectin. Therefore, our data identify NEU3 as a key regulator of the β1 integrin-recycling pathway and FAK/AKT signaling and demonstrate its crucial role in RCC malignancy.
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