title: ABCG2 is required for self-renewal and chemoresistance of CD133-positive human colorectal cancer cells.
abstract: There is increasing evidence supporting the cancer stem cell (CSC) hypothesis, which suggests that a population of tumor cells with stem cell characteristics is responsible for tumor growth, resistance, and recurrence as well as drug resistance. In colorectal cancer, the CD133 antigen defines distinct cell subpopulations that are rich in tumor-initiating cells; however, the drug resistance properties of these CD133-positive cells have not been well defined. The breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2) is present on the plasma membrane of many types of human cancer cells and contributes to multidrug resistance during chemotherapy. The results of the present study showed that ABCG2 is expressed in CD133-positive CSCs from human colorectal tumors. Furthermore, the downregulation of ABCG2 expression inhibited the self-renewal capacity of these cells, and significantly enhanced the efficacy of chemotherapy-induced apoptosis in LS174T colon adenocarcinoma cells and CD133-positive colorectal carcinoma cells. Together, these data show that ABCG2 expression correlates with the presence of CD133-positive cancer cells, and thus is a possible therapeutic target for colorectal cancer.
authors.affiliation: Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Science, Peking University Health Science Center, Beijing, 100191, China.|Ningxia Human Stem Cell Institute, the General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Ningxia Human Stem Cell Institute, the General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Ningxia Human Stem Cell Institute, the General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Ningxia Human Stem Cell Institute, the General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Ningxia Human Stem Cell Institute, the General Hospital of Ningxia Medical University, Yinchuan, 750004, China. yinxueyang196@163.com.
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, School of Basic Medical Science, Peking University Health Science Center, Beijing, 100191, China. Hongquan.Zhang@bjmu.edu.cn.
authors.forename: Hongquan
authors.identifier: http://orcid.org/0000-0002-4885-3104
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics* / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil
keywords: ABCG2; CD133+; Chemoresistance; Colorectal cancer cell; Self-renewal