Journal
CANCER LETTERS
Volume 501, Issue -, Pages 263-276Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.10.048
Keywords
Immunoglobulin-like transcript 3; Migration and invasion; Angiogenesis; Non-small cell lung cancer; Apolipoprotein E
Categories
Funding
- Academic Promotion Program of Shandong First Medical University [2019QL025]
- National Major Science and Technology Projects of China [2020ZX09201025]
- Natural Science Foundation of Shandong Province [ZR2019MH042]
- Jinan Science and Technology Program [201805064, 201907110]
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ILT3, an immunosuppressive molecule, is enriched in NSCLC cells and promotes tumor cell migration, invasion, and angiogenesis, potentially serving as a poor prognostic factor for NSCLC patients.
Immunoglobulin-like transcript (ILT) 3 is an immunosuppressive molecule that negatively regulates myeloid cell activation. ILT3 overexpression in tumor cells induces immune escape of solid tumors and facilitates invasion of monocytic acute myeloid leukemia cells. However, the expression and function of ILT3 in non-small cell lung cancer (NSCLC) cells remain elusive. Herein, we found that ILT3 was enriched in human NSCLC cells, and predicted advanced disease and poor overall survival. ILT3 overexpression enhanced the migration and invasion of NSCLC cells and tubule formation of human umbilical vein endothelial cells by upregulating and interacting with its ligand apolipoprotein E (ApoE) in vitro. Mechanistically, ILT3 recruited SHP2 and SHIP1, and subsequently activated ERK1/2 signaling mediating epithelial-mesenchymal transition (EMT) and increasing vascular endothelial growth factor (VEGF)-A expression in NSCLC cells, which are responsible for tumor cell motility and angiogenesis, respectively. Using murine metastasis models, we further confirmed ILT3 promoted NSCLC metastasis and explored the exact correlation of ILT3 with ApoE, EMT, and VEGF-A in vivo. These results unraveled novel mechanisms for ILT3-induced tumor progression and proposed ILT3 as a potential therapeutic target and prognostic biomarker for NSCLC patients.
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