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

被引：22

作者：

Xu, Dan-dan ^{[1
,2
,3
]}

Wang, Ying ^{[1
]}

Zhou, Peng-jun ^{[1
]}

Qin, Shu-rong ^{[1
]}

Zhang, Rong ^{[4
,5
]}

Zhang, Yi ^{[6
]}

Xue, Xue ^{[3
]}

Wang, Jianping ^{[3
]}

Wang, Xia ^{[3
]}

Chen, Hong-ce ^{[7
]}

Wang, Xiao ^{[1
]}

Pan, Yu-wei ^{[8
]}

Zhang, Li ^{[1
]}

Yan, Hai-zhao ^{[9
]}

Liu, Qiu-ying ^{[1
]}

Liu, Zhong ^{[1
]}

Chen, Su-hong ^{[1
,3
]}

Chen, Hong-yuan ^{[7
]}

Wang, Yi-fei ^{[1
,2
]}

机构：

[1] Jinan Univ, Coll Life Sci & Technol, Guangzhou, Guangdong, Peoples R China

[2] Jinan Univ, Guangdong Prov Key Lab Bioengn Med, Guangzhou, Guangdong, Peoples R China

[3] Guangdong Food & Drug Vocat Coll, Guangzhou, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China

[5] Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China

[6] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Canc Ctr, Washington, DC 20037 USA

[7] Guangdong Pharmaceut Univ, Sch Basic Course, Dept Pathogen Biol & Immunol, Guangzhou, Guangdong, Peoples R China

[8] Jinan Univ, Coll Pharm, Guangzhou, Guangdong, Peoples R China

[9] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Kofu, Yamanashi, Japan

来源：

FRONTIERS IN PHARMACOLOGY | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

Nanog; IGF2; IGF1R; proliferation; leukemia stem cells; GROWTH-FACTOR RECEPTOR; SELF-RENEWAL; TUMOR-GROWTH; I RECEPTOR; IGF-II; NANOG; EXPRESSION; PLURIPOTENCY; NETWORK; OCT4;

D O I：

10.3389/fphar.2018.00687

中图分类号：

R9 [药学];

学科分类号：

1007 ;

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.

引用

页数：14