ArticleProceedings of the National Academy of Sciences of the United States of America2013
Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 146 citations in OpenAlex.
- Anticancer Effects of Cucurbitacin B and Meleagrin Associated with TYRO3 Downregulation in Colorectal Cancer Cells.International journal of molecular sciences · 2026Article
- TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers.Cancer medicine · 2026Article
- A MERTK-Targeting Antibody-Drug Conjugate Selectively Depletes M2 Tumor-Associated Macrophages and MERTK-Expressing Cancer Cells.Cancer research · 2026Article
- Impaired Macrophage Efferocytosis: Shared Mechanisms and Therapeutic Implications in Immune-Mediated Inflammatory Diseases.Journal of inflammation research · 2026Review
- From pathogenesis to therapeutic targeting: new insight into TAM receptors in rheumatoid arthritis.Cell & bioscience · 2025Review
- Variation in virion phosphatidylserine content drives differential GAS6 binding among closely related flaviviruses.Journal of virology · 2025Article
- Tetrahedral Framework Nucleic Acid Relieves Sepsis-Induced Intestinal Injury by Regulating M2 Macrophages.Cell proliferation · 2025Article
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate.Aging cell · 2025Review
- Emerging AXL Inhibitors in Oncology: Chemical and Biological Advances in Targeted Cancer Therapy.Anti-cancer agents in medicinal chemistry · 2025Review
- Exploring and validating the necroptotic gene regulation and related lncRNA mechanisms in colon adenocarcinoma based on multi-dimensional data.Scientific reports · 2024Article
- Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis?Current issues in molecular biology · 2024Review
- In the Eyes of the Beholder-NewInternational journal of molecular sciences · 2024Review
- Tumor-Extrinsic Axl Expression Shapes an Inflammatory Microenvironment Independent of Tumor Cell Promoting Axl Signaling in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Article
- Non-professional efferocytosis of Salmonella-infected intestinal epithelial cells in the neonatal host.The Journal of experimental medicine · 2024Article
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
- Review
- YAP1 expression in colorectal cancer confers the aggressive phenotypes via its target genes.Cell cycle (Georgetown, Tex.) · 2024Article
- Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms.Frontiers in immunology · 2024Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The receptor tyrosine kinases Axl and Mer, belonging to the Tyro3, Axl and Mer (TAM) receptor family, are expressed in a number of tumor cells and have well-characterized oncogenic roles. The therapeutic targeting of these kinases is considered an anticancer strategy, and various inhibitors are currently under development. At the same time, Axl and Mer are expressed in dendritic cells and macrophages and have an essential function in limiting inflammation. Inflammation is an enabling characteristic of multiple cancer hallmarks. These contrasting oncogenic and anti-inflammatory functions of Axl and Mer posit a potential paradox in terms of anticancer therapy. Here we demonstrate that azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced inflammation-associated cancer is exacerbated in mice lacking Axl and Mer. Ablation of Axl and Mer signaling is associated with increased production of proinflammatory cytokines and failure to clear apoptotic neutrophils in the intestinal lamina propria, thereby favoring a tumor-promoting environment. Interestingly, loss of these genes in the hematopoietic compartment is not associated with increased colitis. Axl and Mer are expressed in radioresistant intestinal macrophages, and the loss of these genes is associated with an increased inflammatory signature in this compartment. Our results raise the possibility of potential adverse effects of systemic anticancer therapies with Axl and Mer inhibitors, and underscore the importance of understanding their tissue and cell type-specific functions in 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.