ArticleThe Biochemical journal2020
SLC6A14, a Na+/Cl--coupled amino acid transporter, functions as a tumor promoter in colon and is a target for Wnt signaling.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 55 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Emerging roles of SLC6A14 in digestive system diseases: from amino acid transport to therapeutic targeting.Molecular biology reports · 2026Review
- Dual targeting of SLC6A14 and autophagy/macropinocytosis enhances therapeutic efficacy in pancreatic ductal adenocarcinoma.The Biochemical journal · 2026Article
- Article
- Machine learning-based identification of a metabolic cell death gene signature for assessing disease activity and immunological landscape in inflammatory bowel disease.Scientific reports · 2026Article
- Bronchial epithelial-derived exosomal SLC6A14 promotes airway inflammation and mucus hypersecretion via the ZFP36L1/IL-8 axis.Functional & integrative genomics · 2026Article
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Bacterial colonized melanoma skin models allow to study host-microbe interactionsFrontiers in microbiology · 2026Article
- Gut microbial metabolites in colorectal cancer: dual roles in tumorigenesis, immune crosstalk, and therapeutic innovation.Frontiers in cellular and infection microbiology · 2026Review
- SLC6A14-mediated glutamine promotes SYTL4-CXCL8 axis activation to drive gemcitabine resistance and immune evasion in pancreatic cancer.Experimental & molecular medicine · 2025Article
- A new combined prognostic model involvingTranslational cancer research · 2025Article
- α-Methyltryptophan mitigates cognitive impairment in db/db mice: involvement of gut-brain metabolic remodeling.Nutrition & metabolism · 2025Article
- Evolutionary conservation and cancer implications of the WNT signaling pathway.Medical oncology (Northwood, London, England) · 2025Review
- Charged multivesicular body protein 7 was identified as a prognostic biomarker correlated with metastasis in colorectal cancer.World journal of gastrointestinal oncology · 2025Article
- The Solute Carrier Superfamily as Therapeutic Targets in Pancreatic Ductal Adenocarcinoma.Genes · 2025Article
- Nanomedicine innovations in colon and rectal cancer: advances in targeted drug and gene delivery systems.Medical oncology (Northwood, London, England) · 2025Review
- The Role of Reactive Oxygen Species in Colorectal Cancer Initiation and Progression: Perspectives on Theranostic Approaches.Cancers · 2025Review
- A Review on the Role of Human Solute Carriers Transporters in Cancer.Health science reports · 2025Article
- The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling.Frontiers in immunology · 2025Review
- Identification of the shared gene signatures in retinoblastoma and osteosarcoma by machine learning.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SLC6A14 is a Na+/Cl--coupled transporter for neutral and cationic amino acids. It is expressed at basal levels in the normal colon but is up-regulated in colon cancer. However, the relevance of this up-regulation to cancer progression and the mechanisms involved in the up-regulation remain unknown. Here, we show that SLC6A14 is essential for colon cancer and that its up-regulation involves, at least partly, Wnt signaling. The up-regulation of the transporter is evident in most human colon cancer cell lines and also in a majority of patient-derived xenografts. These findings are supported by publicly available TCGA (The Cancer Genome Atlas) database. Treatment of colon cancer cells with α-methyltryptophan (α-MT), a blocker of SLC6A14, induces amino acid deprivation, decreases mTOR activity, increases autophagy, promotes apoptosis, and suppresses cell proliferation and invasion. In xenograft and syngeneic mouse tumor models, silencing of SLC6A14 by shRNA or blocking its function by α-MT reduces tumor growth. Similarly, the deletion of Slc6a14 in mice protects against colon cancer in two different experimental models (inflammation-associated colon cancer and genetically driven colon cancer). In colon cancer cells, expression of the transporter is reduced by Wnt antagonist or by silencing of β-catenin whereas Wnt agonist or overexpression of β-catenin shows the opposite effect. Finally, SLC6A14 as a target for β-catenin is confirmed by chromatin immunoprecipitation. These studies demonstrate that SLC6A14 plays a critical role in the promotion of colon cancer and that its up-regulation in cancer involves Wnt signaling. These findings identify SLC6A14 as a promising drug target for the treatment of colon 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.