ArticleCancers2019
Tumour-Secreted Protein S (ProS1) Activates a Tyro3-Erk Signalling Axis and Protects Cancer Cells from Apoptosis.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers.Cancer medicine · 2026Article
- ProS1-MerTK signaling in CD4 T cells: implications for TIL expansion and functionality.Oncoimmunology · 2025Article
- Prognostic Significance and Immune Landscape of an Efferocytosis-Related Gene Signature in Bladder Cancer.Biochemical genetics · 2025Article
- Calumenin, A Calcium-Binding Modulatory Protein, Effective in Pathological Calcifications and Cancers, With Therapeutic Application Promise.FASEB bioAdvances · 2025Review
- A Computational Approach to Characterize the Protein S-Mer Tyrosine Kinase (PROS1-MERTK) Protein-Protein Interaction Dynamics.Cell biochemistry and biophysics · 2025Article
- Functions of TAM Receptors and Ligands Protein S and Gas6 in Atherosclerosis and Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Article
- E3 ubiquitin ligase BTBD3 inhibits tumorigenesis of colorectal cancer by regulating the TYRO3/Wnt/β-catenin signaling axis.Cancer cell international · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- From MASH to HCC: the role of Gas6/TAM receptors.Frontiers in immunology · 2024Review
- Stemness signature and targeted therapeutic drugs identification for Triple Negative Breast Cancer.Scientific data · 2023Article
- The impact of inflammation and acute phase activation in cancer cachexia.Frontiers in immunology · 2023Review
- Tyro3 Targeting as a Radiosensitizing Strategy in Bladder Cancer through Cell Cycle Dysregulation.International journal of molecular sciences · 2022Article
- The first laminin G-like domain of protein S is essential for binding and activation of Tyro3 receptor and intracellular signalling.Biochemistry and biophysics reports · 2022Article
- PROS1 shapes the immune-suppressive tumor microenvironment and predicts poor prognosis in glioma.Frontiers in immunology · 2022Article
- Identification of signalling pathways activated by Tyro3 that promote cell survival, proliferation and invasiveness in human cancer cells.Biochemistry and biophysics reports · 2021Article
- Imbalance in Coagulation/Fibrinolysis Inhibitors Resulting in Extravascular Thrombin Generation in Gliomas of Varying Levels of Malignancy.Biomolecules · 2021Article
- G-749 Promotes Receptor Tyrosine Kinase TYRO3 Degradation and Induces Apoptosis in Both Colon Cancer Cell Lines and Xenograft Mouse Models.Frontiers in pharmacology · 2021Article
- Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The TAM subfamily (Tyro3, Axl, MerTK) of receptor tyrosine kinases are implicated in several cancers, where they have been shown to support primary tumorigenesis as well as secondary resistance to cancer therapies. Relatively little is known about the oncogenic role of Tyro3, including its ligand selectivity and signalling in cancer cells. Tyro3 showed widespread protein and mRNA expression in a variety of human cancer cell lines. In SCC-25 head and neck cancer cells expressing both Tyro3 and Axl, Western blotting showed that both natural TAM ligands ProS1 and Gas6 rapidly stimulated Tyro3 and Erk kinase phosphorylation, with ProS1 eliciting a greater effect. In contrast, Gas6 was the sole stimulator of Axl and Akt kinase phosphorylation. In MGH-U3 bladder cancer cells, which express Tyro3 alone, ProS1 was again the stronger stimulator of Tyro3 and Erk stimulation but additionally stimulated Akt phosphorylation. Conditioned medium from ProS1-secreting 786-0 kidney cancer cells replicated the kinase activation effects of recombinant ProS1 in SCC-25 cells, with specificity confirmed by ProS1 ligand traps and warfarin. In addition, ProS1 protected cancer cells from acute apoptosis induced by staurosporine, as well as additionally, long-term serum starvation-induced apoptosis in MGH-U3 cells (Tyro3 only), which reflects its additional coupling to Akt signalling in these cells. In conclusion, we have shown that ProS1 is a tumour-derived functional ligand for Tyro3 that supports cancer cell survival. Furthermore, the ProS1-Tyro3 interaction is primarily coupled to Erk signalling although it displays signalling diversity dependent upon its representative expression as a TAM receptor in tumour cells.
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