The IGF2/IGF1R/Nanog Signaling Pathway Regulates the Proliferation of Acute Myeloid Leukemia Stem Cells

Frontiers in Pharmacology

Li Zhang¹  Xiao Wang¹  Peng-jun Zhou¹  Qiu-ying Liu¹  Ying Wang¹  Shu-rong Qin¹  Zhong Liu¹  Yu-wei Pan²  Yi Zhang³  Hong-ce Chen⁴  Hong-yuan Chen⁴  Xue Xue⁵  Su-hong Chen⁵  Dan-dan Xu⁵  Xia Wang⁵  Jianping Wang⁵  Yi-fei Wang⁶  Hai-zhao Yan⁷  Rong Zhang⁸ 

[1] College of Life Science and Technology, Jinan University, Guangzhou, China;College of Pharmacy, Jinan University, Guangzhou, China;Department of Biochemistry and Molecular Medicine, Cancer Center, George Washington University School of Medicine and Health Sciences, Washington, DC, United States;Department of Pathogen Biology and Immunology, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou, China;Guangdong Food and Drug Vocational College, Guangzhou, China;Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, China;Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Kofu, Japan;State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China;

关键词: Nanog;    IGF2;    IGF1R;    proliferation;    leukemia stem cells;   

DOI  :  10.3389/fphar.2018.00687

来源: DOAJ

【 摘 要 】

Acute myeloid leukemia is an aggressive disease characterized by clonal proliferation and differentiation into immature hematopoietic cells of dysfunctional myeloid precursors. Accumulating evidence shows that CD34+CD38- leukemia stem cells (LSCs) are responsible for drug resistance, metastasis, and relapse of leukemia. In this study, we found that Nanog, a transcription factor in stem cells, is significantly overexpressed in CD34+ populations from patients with acute myeloid leukemia and in LSCs from leukemia cell lines. Our data demonstrate that the knockdown of Nanog inhibited proliferation and induced cell cycle arrest and cell apoptosis. Moreover, Nanog silencing suppressed the leukemogenesis of LSCs in mice. In addition, we found that these functions of Nanog were regulated by the insulin-like growth factor receptor (IGF1R) signaling pathway. Nanog overexpression rescued the colony formation ability of LSCs treated with picropodophyllin (PPP), an IGF1R inhibitor. By contrast, knockdown of Nanog abolished the effects of IGF2 on the colony formation ability of these LSCs. These findings suggest that the IGF2/IGF1R/Nanog signaling pathway plays a critical role in LSC proliferation.

【 授权许可】

Unknown