Research Papers:

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 and Junke Zheng _

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Oncotarget. 2015; 6:21004-21015. https://doi.org/10.18632/oncotarget.4217

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Xiaoye Liu1,2,3,*, Xiaoting Yu4,*, Jingjing Xie5, Mengna Zhan6, Zhuo Yu3, Li Xie3, Hongxiang Zeng3, Feifei Zhang3, Guoqiang Chen1,3, Xianghua Yi4 and Junke Zheng2,3

1 Institute of Health Sciences, Shanghai Institute for Biological Sciences, University of Chinese Academy of Science, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China

2 Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China

3 Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

4 Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China

5 Bingzhou Medical University, Taishan Scholar Program, Yantai, China

6 Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

* These authors have contributed equally to this paper

Correspondence to:

Junke Zheng, email:

Xianghua Yi, email:

Guoqiang Chen, email:

Keywords: ANGPTL2/LILRB2 signaling, lung cancer, metastasis, CaMK1

Received: December 31, 2014 Accepted: May 10, 2015 Published: May 20, 2015


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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