ANGPTL2/LILRB2 signaling promotes the propagation of lung cancer cells

Xiaoye Liu, Xiaoting Yu, Jingjing Xie, Mengna Zhan, Zhuo Yu, Li Xie, Hongxiang Zeng, Feifei Zhang, Guoqiang Chen, Xianghua Yi, Junke Zheng

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21004-21015
Number of pages12
JournalOncotarget
Volume6
Issue number25
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • ANGPTL2/LILRB2 signaling
  • CaMK1
  • Lung cancer
  • Metastasis

ASJC Scopus subject areas

  • Oncology

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