Osteopontin induces autophagy to promote chemo-resistance in human hepatocellular carcinoma cells

被引：80

作者：

Liu, Guoke ^{[1
]}

Fan, Xiaoyu ^{[2
]}

Tang, Min ^{[1
]}

Chen, Rui ^{[1
]}

Wang, Hao ^{[1
]}

Jia, Rongjie ^{[1
]}

Zhou, Xuyu ^{[3
]}

Jing, Wei ^{[3
]}

Wang, Huajing ^{[1
]}

Yang, Yang ^{[1
]}

Yin, Fan ^{[4
]}

Wei, Huafeng ^{[4
]}

Li, Bohua ^{[1
]}

Zhao, Jian ^{[1
]}

机构：

[1] Second Mil Med Univ, Int Joint Canc Inst, 800 Xiangyin Rd,Lib Bldg 9-11th Floor, Shanghai 200433, Peoples R China

[2] Lanzhou Gen Hosp, Dept Pathol, South Binhe Rd, Lanzhou 730050, Peoples R China

[3] Second Mil Med Univ, Changhai Hosp, Changhai Rd, Shanghai 200433, Peoples R China

[4] Peoples Liberat Army Gen Hosp, Ctr Canc, Key Lab, PIA Postgrad Sch Med, 28 Fuxing Rd, Beijing 100853, Peoples R China

来源：

CANCER LETTERS | 2016年 / 383卷 / 02期

关键词：

Osteopontin; Autophagy; FoxO3a; Chemo-resistance; Stem-like phenotype; CANCER STEM-CELLS; SUPPRESSES TUMOR-GROWTH; INITIATING CELLS; IN-VIVO; SURVIVAL; METASTASIS; TRANSITION; EXPRESSION; PATHWAY; MICROENVIRONMENT;

D O I：

10.1016/j.canlet.2016.09.033

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hepatocellular carcinoma (HCC) is a major health burden worldwide for its high incidence and mortality. Osteopontin (OPN) is a chemokine-like, matricellular phosphoglycoprotein whose expression is elevated in various types of cancer including HCC. OPN has been shown to be involved in tumorigenesis, chemoresistance, metastasis and sustaining stem-like properties of cancer cells. Autophagy is a cellular process by which cytoplasmic components are degraded and recycled for maintaining cellular homeostasis. There is increasing evidence supports that autophagy plays a critical role for stem-like properties and chemo-resistance of cancer cells. However, the relationship between OPN and autophagy in maintaining cancer stem-like properties and chemo-resistance is yet to be clarified. Herein, we found that secreted OPN induced autophagy via binding with its receptor integrin alpha v beta 3 and sustaining FoxO3a stability. OPN-elicited autophagy could promote cancer cell survival and resistance to chemotherapy drugs, as well as stem-like properties. Our findings indicated that OPN was capable of promoting chemo-resistance of HCCs via autophagy, which might provide a new strategy for the treatment of HCC. (C) 2016 Published by Elsevier Ireland Ltd.

引用

页码：171 / 182

页数：12

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