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Updated: Mar 24, 2026
Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
GAS6 potentiates tumor progression through modulating suppressive microenvironments
Shaoteng Lu1, Hangxu Liu2, Fujie Zhang1
1National Key Laboratory of Immunity and Inflammation, Naval Medical University/Second Military Medical University Shanghai 200433, China.
Abstract:
Although growth arrest-specific 6 (GAS6), the principal ligand of the TAM receptors (TYRO3, AXL, and MERTK), acts as a central coordinator of efferocytosis, no pan-cancer analysis has been conducted. We thus first analyzed GAS6 across thirty-three tumors based on the datasets on TCGA (The Cancer Genome Atlas), TCGA-XENA (UCSC Xena), and other publicly available repositories. We observed a correlation of aberrant expression of GAS6 with malignant transformation and cancer progression, which strongly predicts worse overall survival in multiple malignancies. Transcriptomic deconvolution revealed a clear positive correlation between GAS6 levels and macrophage infiltration and polarization. Our study systematically revealed the evidence establishing GAS6 as an oncogenic driver and a regulator of the immunosuppressive microenvironment across human cancers. These findings furnish a mechanistic rationale for therapeutically targeting the GAS6/TAM axis to subvert immune tolerance and potentiate chemoradiation.
Insights
Growth arrest-specific 6 (GAS6) is linked to cancer progression and poor survival across many cancer types. Targeting the GAS6/TAM pathway may overcome immune tolerance and enhance cancer treatments.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Growth arrest-specific 6 (GAS6) is the primary ligand for TAM receptors (TYRO3, AXL, MERTK), crucial for efferocytosis.
- A comprehensive pan-cancer analysis of GAS6's role has been lacking.
Purpose of the Study:
- To investigate the pan-cancer expression of GAS6 and its correlation with clinical outcomes.
- To explore the relationship between GAS6 levels, tumor-infiltrating macrophages, and the tumor microenvironment.
Main Methods:
- Analysis of GAS6 expression across 33 tumor types using TCGA and TCGA-XENA datasets.
- Transcriptomic deconvolution to assess macrophage infiltration and polarization.
- Correlation analysis between GAS6 expression, survival data, and immune cell infiltration.
Main Results:
- Aberrant GAS6 expression was observed in conjunction with malignant transformation and cancer progression.
- Elevated GAS6 levels significantly predicted worse overall survival in multiple malignancies.
- GAS6 expression positively correlated with increased macrophage infiltration and M2 polarization.
Conclusions:
- GAS6 acts as an oncogenic driver and a key regulator of the immunosuppressive tumor microenvironment in human cancers.
- Targeting the GAS6/TAM axis presents a potential therapeutic strategy to enhance anti-cancer immunity and treatment efficacy.
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