Journal
ONCOTARGET
Volume 6, Issue 25, Pages 21004-21015Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4217
Keywords
ANGPTL2/LILRB2 signaling; lung cancer; metastasis; CaMK1
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Funding
- Pujiang Program [13PJ1405600]
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
- National Natural Science Foundation of China [81370654]
- 1000-Youth Elite Program
- Taishan Scholar Immunology Program
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Immune inhibitory receptors expressed on various types of immune cells deliver inhibitory signals that maintain the homeostasis of the immune system. Recently we demonstrated that leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) and its murine homolog, paired immunoglobulin-like receptor B (PIRB), are expressed on hematopoietic stem cells and acute myeloid leukemia stem cells and function in maintenance of stemness. Herein, we determined that both LILRB2 and its soluble ligand ANGPTL2 are highly expressed in non-small cell lung cancer (NSCLC) samples, and levels are adversely related to patient prognosis. Inhibition of LILRB2 expression in NSCLC cell lines, such as A549 cells, resulted in a dramatic decrease in proliferation, colony formation, and migration. Mechanistic analyses indicated that ANGPTL2 binds LILRB2 to support the growth of lung cancer cells and that the SHP2/CaMK1/CREB axis controls the proliferation of lung cancer cell lines. Our results suggest that signaling involving ANGPTL2 and LILRB2 is important for lung cancer development and represents a novel target for treatment of this type of cancer.
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