ArticleMolecular cancer2013
CD98hc (SLC3A2) drives integrin-dependent renal cancer cell behavior.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Collagen I promotes cancer cell survival via amino acid import and mTORC1/S6 activation.PLoS biology · 2026Article
- AGR2 promotes tumor progression by regulating macrophage polarization via the CD98hc-xCT/p-ERK pathway.Frontiers in immunology · 2026Article
- Elevated SLC3A2 Expression Promotes the Progression of Gliomas and Enhances Ferroptosis Resistance through the AKT/NRF2/GPX4 Axis.Cancer research and treatment · 2026Article
- Unveiling Metabolic Signatures as Potential Biomarkers in Common Cancers: Insights from Lung, Breast, Colorectal, Liver, and Gastric Tumours.Biomolecules · 2025Review
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- Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer.Frontiers in immunology · 2025Article
- Prognostic and therapeutic model based on disulfidptosis-related genes for patients with clear cell renal cell carcinoma.Heliyon · 2024Article
- Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.Molecular metabolism · 2024Review
- Metabolic Responses of Lung Adenocarcinoma Cells to Survive under Stressful Conditions Associated with Tumor Microenvironment.Metabolites · 2024Article
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- SLC3A2 promotes tumor-associated macrophage polarization through metabolic reprogramming in lung cancer.Cancer science · 2023Article
- CD98 heavy chain as a prognostic biomarker and target for cancer treatment.Frontiers in oncology · 2023Review
- CD98hc as a marker of radiotherapy-resistant cancer stem cells in head and neck squamous cell carcinoma.Archives of medical science : AMS · 2023Article
- Article
- CD98hc has a pivotal role in maintaining the immuno-barrier integrity of basal layer cells in esophageal epithelium.Cancer cell international · 2022Article
- Article
- Expression of CD98hc in Pancreatic Cancer and Its Role in Cancer Cell Behavior.Journal of Cancer · 2022Article
- The Ectodomains of rBAT and 4F2hc Are Fake or Orphan α-Glucosidases.Molecules (Basel, Switzerland) · 2021Review
- Oncogenic transformation of NIH/3T3 cells by the overexpression of L-type amino acid transporter 1, a promising anti-cancer target.Oncotarget · 2021Article
- Identification of Tumor Microenvironment-Related Alternative Splicing Events to Predict the Prognosis of Endometrial Cancer.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOverexpression of CD98hc (SLC3A2) occurs in a variety of cancers and is suspected to contribute to tumor growth. CD98, a heterodimeric transmembrane protein, physically associates with certain integrin β subunit cytoplasmic domains via its heavy chain, CD98hc. CD98hc regulates adhesion-induced intracellular signal transduction via integrins, thereby, affecting cell proliferation and clonal expansion. Disruption of CD98hc led to embryonic lethality in mice (E 3.5 and E 9.5) and CD98hc -/- embryonic stem cell transplantation failed to form teratomas, while CD98hc over-expression in somatic cells resulted in anchorage-independent growth. However, it is unclear whether interference with CD98hc expression tumor cell behavior.
methodsRenal cell cancer cell lines have been used to determine the effect of CD98hc expression on cancer cell behavior using cell adhesion, cell trans-migration and cell spreading assays. Flow cytometric analysis was performed to study the rate of apoptosis after detachment or serum starvation. shRNA-lentiviral constructs were used to stably knockdown or reconstitute full length or mutated CD98hc. The role of CD98 as a promotor of tumorigenesis was evaluated using an in in vivo tumor transplantation animal model. Immunohistochemical analysis was performed to analyze cell proliferation and CD98 expression in tumors.
resultsThis report shows that CD98hc silencing in clear cell renal cancer cells reverts certain characteristics of tumorigenesis, including cell spreading, migration, proliferation and survival in vitro, and tumor growth in vivo. Acquisition of tumorigenic characteristics in clear cell renal cancer cells occurred through the integrin binding domain of CD98hc. A CD98hc/integrin interaction was required for adhesion-induced sustained FAK phosphorylation and activation of the major downstream signaling pathways PI3k/Akt and MEK/ERK, while overexpression of a constitutive active form of FAK rescued the CD98hc deficiency.
conclusionsIn this study we demonstrate that loss of CD98hc blocks tumorigenic potential in renal cell cancer.
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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.