title: Osteopontin induces autophagy to promote chemo-resistance in human hepatocellular carcinoma cells.
abstract: 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, chemo-resistance, 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 αvβ3 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.
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: liugk01@163.com.
authors.forename: Guoke
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pathology, Lanzhou General Hospital, South Binhe Road, Lanzhou 730050, People's Republic of China. Electronic address: fan_xyxy@126.com.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Fan
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: ttangmin@sina.com.
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: reachy_chen@hotmail.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: whdoublehai@126.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: jiarongjie1221@126.com.
authors.forename: Rongjie
authors.initials: R
authors.lastname: Jia
authors.affiliation: Changhai Hospital, The Second Military Medical University, Changhai Road, Shanghai 200433, People's Republic of China. Electronic address: zhouxuyuch@163.com.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Changhai Hospital, The Second Military Medical University, Changhai Road, Shanghai 200433, People's Republic of China. Electronic address: jingwei7777@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Jing
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: jwhuajing@163.com.
authors.forename: Huajing
authors.initials: H
authors.lastname: Wang
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: bbyy125@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: PLA General Hospital Cancer Center Key Lab, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing 100853, People's Republic of China. Electronic address: ying2124@sina.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Yin
authors.affiliation: PLA General Hospital Cancer Center Key Lab, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing 100853, People's Republic of China. Electronic address: foxp3_smmu@163.com.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wei
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: bohuali1020@163.com.
authors.forename: Bohua
authors.initials: B
authors.lastname: Li
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. Electronic address: zhaojian@smmu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D055550:Protein Stability; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D039302:Integrin alphaVbeta3; C506895:SPP1 protein, human; D053495:Osteopontin; D015251:Epirubicin; D002945:Cisplatin
keywords: Autophagy; Chemo-resistance; FoxO3a; Osteopontin; Stem-like phenotype