DOI: 10.1634/stemcells.2005-0282. Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System

Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System

10.1634/stemcells.2005-0282

Crossref journal-article

Oxford University Press (OUP)

Stem Cells (286)

Abstract

AbstractA subset of stem cells, termed “side population” (SP) cells, has been identified and characterized in several mammalian tissues and cell lines. However, SP cells have never been identified or isolated from gastrointestinal cancers. We used flow cytometry and the DNA-binding dye Hoechst 33342 to isolate SP cells from various human gastrointestinal system cancer cell lines. Fifteen of sixteen cancer cell lines from the gastrointestinal system contained 0.3%–2.2% SP cells. Next, we used an oligonucleotide microarray to analyze differentially expressed genes between SP and non-SP cells of hepatoma HuH7. The expression of GATA6, which is associated with embryonic development and hepatocytic differentiation, was significantly upregulated in HuH7 SP cells. The expression of ABCG2, ABCB1, and CEACAM6, which are associated with chemoresistance, was also significantly increased in SP cells. In addition, some epithelial markers and mesenchymal markers were overexpressed in SP cells. Reverse transcription-polymerase chain reaction and immunocytochemical staining validated these results and suggested a multilineage potential for HuH7 SP cells. In hepatoma HuH7 and colorectal SW480 cell lines, SP cells showed evidence for self-renewal, generating both SP and non-SP cells. Finally, chemoresistance to anticancer agents, including doxorubicin, 5-fluorouracil, and gemcitabine, were compared between HuH7 SP and non-SP cells using an ATP bioluminescence assay. The HuH7 SP cells expressed a higher resistance to doxorubicin, 5-fluorouracil, and gemcitabine compared with non-SP cells. These findings demonstrate that cancers of the gastrointestinal system do contain SP cells that show some characteristics of so-called stem cells.

Bibliography

Haraguchi, N., Utsunomiya, T., Inoue, H., Tanaka, F., Mimori, K., Barnard, G. F., & Mori, M. (2005). Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System. Stem Cells, 24(3), 506â513.

Authors 7

Naotsugu Haraguchi (first)
Tohru Utsunomiya (additional)
Hiroshi Inoue (additional)
Fumiaki Tanaka (additional)
Koshi Mimori (additional)
Graham F. Barnard (additional)
Masaki Mori (additional)

References 30 Referenced 439

10.1038/35102167 / Nature / Stem cell, cancer, and cancer stem cell by Reya (2001)
10.1038/nrc1232 / Nat Rev Cancer / Applying the principles of stem-cell biology to cancer by Pardal (2003)
10.1038/nature03100 / Nature / Tissue repair and stem cell renewal in carcinogenesis by Beachy (2004)
10.1182/blood.V98.4.1166 / Blood / A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia by Wulf (2001)
10.1038/367645a0 / Nature / A cell initiating human acute myeloid leukemia after transplantation into SCID mice by Lapidot (1994)
10.1038/nm0797-730 / Nat Med / Human acute leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell by Bonnet (1997)
10.1073/pnas.0530291100 / Proc Natl Acad Sci U S A / Prospective identification of tumorigenic breast cancer cells by Al-Hajj (2003)
10.1073/pnas.0307618100 / Proc Natl Acad Sci U S A / Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line by Kondo (2004)
10.1073/pnas.0400067101 / Proc Natl Acad Sci U S A / A distinct “side population” of cells with high drug efflux capacity in human tumor cells by Hirschmann-Jax (2004)
10.1073/pnas.2036535100 / Proc Natl Acad Sci U S A / Cancerous stem cells can arise from pediatric brain tumors by Hemmati (2003)
10.1038/sj.onc.1208311 / Oncogene / Isolation of cancer stem cells from adult glioblastoma multiform by Yuan (2004)
10.1038/nature03128 / Nature / Identification of human brain tumour initiating cells by Singh (2004)
10.1038/nm1297-1337 / Nat Med / Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species by Goodell (1997)
10.1016/j.jhep.2004.05.015 / J Hepatol / A gene-expression signature can quantify the degree of rat hepatic fibrosis by Utsunomiya (2004)
10.1158/0008-5472.401.65.2 / Cancer Res / Global analysis of altered gene-expressions during the process of esophageal squamous cell carcinogenesis in the rat: A study combined with a laser microdissection and a cDNA microarray by Nishida (2005)
10.1038/ng1201-365 / Nat Genet / Minimum information about a microarray experiment (MIAME)-toward standards for microarray data by Brazma (2001)
10.1053/jhep.2000.20349 / Hepatology / Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver by Suzuki (2000)
{'key': '2021122214330102500_bib18', 'first-page': '5276', 'article-title': 'Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: Clinical correlation for cisplatin resistance of ovarian carcinoma', 'volume': '55', 'author': 'Andreotti', 'year': '1995', 'journal-title': 'Cancer Res'} / Cancer Res / Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: Clinical correlation for cisplatin resistance of ovarian carcinoma by Andreotti (1995)
10.1002/hep.510230312 / Hepatology / Identification of bipotential progenitor cells in human liver development by Haruna (1996)
10.1053/j.gastro.2004.01.002 / Gastroenterology / Origin and characterization of a human bipotent liver progenitor cell line by Parent (2004)
10.1158/0008-5472.CAN-04-0424 / Cancer Res / A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells by Duxbury (2004)
10.1038/nrc1590 / Nat Rev Cancer / Tumour stem cells and drug resistance by Dean (2005)
10.1093/hmg/ddh331 / Hum Mol Genet / Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839) by Kakiuchi (2004)
10.1038/sj.onc.1207036 / Oncogene / CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability of pancreatic adenocarcinoma cells by Duxbury (2004)
10.1101/gad.12.22.3579 / Genes Dev / GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo by Morrisey (1998)
10.1046/j.1432-0436.2001.680413.x / Differentiation / Genomic expression analysis implicates Wnt signaling pathway and extracellular matrix alterations in hepatic specification and differentiation of murine hepatic stem cells by Plescia (2001)
10.1128/MCB.25.7.2622-2631.2005 / Mol Cell Biol / GATA6 is essential for embryonic development of the liver but dispensable for early heart formation by Zhao (2005)
10.1016/S0012-1606(02)00026-X / Dev Biol / Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6 by Nemer (2003)
10.1074/jbc.M406467200 / J Biol Chem / Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling by Paling (2004)
10.1038/sj.onc.1206483 / Oncogene / Association of vimentin overexpression and hepatocellular carcinoma metastasis by Hu (2004)

Dates

Type	When
Created	19 years, 9 months ago (Oct. 26, 2005, 3:23 a.m.)
Deposited	2 years, 3 months ago (May 5, 2023, 2:07 a.m.)
Indexed	2 months ago (June 25, 2025, 1:49 a.m.)
Issued	19 years, 10 months ago (Oct. 20, 2005)
Published	19 years, 10 months ago (Oct. 20, 2005)
Published Online	19 years, 10 months ago (Oct. 20, 2005)
Published Print	19 years, 5 months ago (March 1, 2006)

Funders 0

None

BibTeX

@article{Haraguchi_2005, title={Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System}, volume={24}, ISSN={1549-4918}, url={http://dx.doi.org/10.1634/stemcells.2005-0282}, DOI={10.1634/stemcells.2005-0282}, number={3}, journal={Stem Cells}, publisher={Oxford University Press (OUP)}, author={Haraguchi, Naotsugu and Utsunomiya, Tohru and Inoue, Hiroshi and Tanaka, Fumiaki and Mimori, Koshi and Barnard, Graham F. and Mori, Masaki}, year={2005}, month=oct, pages={506–513} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        6,
        25
      ]
    ],
    "date-time": "2025-06-25T05:49:43Z",
    "timestamp": 1750830583550
  },
  "reference-count": 30,
  "publisher": "Oxford University Press (OUP)",
  "issue": "3",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2005,
            10,
            20
          ]
        ],
        "date-time": "2005-10-20T00:00:00Z",
        "timestamp": 1129766400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2006,
        3,
        1
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>A subset of stem cells, termed \u201cside population\u201d (SP) cells, has been identified and characterized in several mammalian tissues and cell lines. However, SP cells have never been identified or isolated from gastrointestinal cancers. We used flow cytometry and the DNA-binding dye Hoechst 33342 to isolate SP cells from various human gastrointestinal system cancer cell lines. Fifteen of sixteen cancer cell lines from the gastrointestinal system contained 0.3%\u20132.2% SP cells. Next, we used an oligonucleotide microarray to analyze differentially expressed genes between SP and non-SP cells of hepatoma HuH7. The expression of GATA6, which is associated with embryonic development and hepatocytic differentiation, was significantly upregulated in HuH7 SP cells. The expression of ABCG2, ABCB1, and CEACAM6, which are associated with chemoresistance, was also significantly increased in SP cells. In addition, some epithelial markers and mesenchymal markers were overexpressed in SP cells. Reverse transcription-polymerase chain reaction and immunocytochemical staining validated these results and suggested a multilineage potential for HuH7 SP cells. In hepatoma HuH7 and colorectal SW480 cell lines, SP cells showed evidence for self-renewal, generating both SP and non-SP cells. Finally, chemoresistance to anticancer agents, including doxorubicin, 5-fluorouracil, and gemcitabine, were compared between HuH7 SP and non-SP cells using an ATP bioluminescence assay. The HuH7 SP cells expressed a higher resistance to doxorubicin, 5-fluorouracil, and gemcitabine compared with non-SP cells. These findings demonstrate that cancers of the gastrointestinal system do contain SP cells that show some characteristics of so-called stem cells.</jats:p>",
  "DOI": "10.1634/stemcells.2005-0282",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        10,
        26
      ]
    ],
    "date-time": "2005-10-26T07:23:45Z",
    "timestamp": 1130311425000
  },
  "page": "506-513",
  "source": "Crossref",
  "is-referenced-by-count": 439,
  "title": "Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System",
  "prefix": "10.1093",
  "volume": "24",
  "author": [
    {
      "given": "Naotsugu",
      "family": "Haraguchi",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan"
        }
      ]
    },
    {
      "given": "Tohru",
      "family": "Utsunomiya",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan"
        }
      ]
    },
    {
      "given": "Hiroshi",
      "family": "Inoue",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan"
        }
      ]
    },
    {
      "given": "Fumiaki",
      "family": "Tanaka",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan"
        }
      ]
    },
    {
      "given": "Koshi",
      "family": "Mimori",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan"
        }
      ]
    },
    {
      "given": "Graham F.",
      "family": "Barnard",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA"
        }
      ]
    },
    {
      "given": "Masaki",
      "family": "Mori",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan"
        }
      ]
    }
  ],
  "member": "286",
  "published-online": {
    "date-parts": [
      [
        2005,
        10,
        20
      ]
    ]
  },
  "reference": [
    {
      "key": "2021122214330102500_bib1",
      "doi-asserted-by": "crossref",
      "first-page": "105",
      "DOI": "10.1038/35102167",
      "article-title": "Stem cell, cancer, and cancer stem cell",
      "volume": "414",
      "author": "Reya",
      "year": "2001",
      "journal-title": "Nature"
    },
    {
      "key": "2021122214330102500_bib2",
      "doi-asserted-by": "crossref",
      "first-page": "895",
      "DOI": "10.1038/nrc1232",
      "article-title": "Applying the principles of stem-cell biology to cancer",
      "volume": "3",
      "author": "Pardal",
      "year": "2003",
      "journal-title": "Nat Rev Cancer"
    },
    {
      "key": "2021122214330102500_bib3",
      "doi-asserted-by": "crossref",
      "first-page": "324",
      "DOI": "10.1038/nature03100",
      "article-title": "Tissue repair and stem cell renewal in carcinogenesis",
      "volume": "432",
      "author": "Beachy",
      "year": "2004",
      "journal-title": "Nature"
    },
    {
      "key": "2021122214330102500_bib4",
      "doi-asserted-by": "crossref",
      "first-page": "1166",
      "DOI": "10.1182/blood.V98.4.1166",
      "article-title": "A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia",
      "volume": "98",
      "author": "Wulf",
      "year": "2001",
      "journal-title": "Blood"
    },
    {
      "key": "2021122214330102500_bib5",
      "doi-asserted-by": "crossref",
      "first-page": "645",
      "DOI": "10.1038/367645a0",
      "article-title": "A cell initiating human acute myeloid leukemia after transplantation into SCID mice",
      "volume": "367",
      "author": "Lapidot",
      "year": "1994",
      "journal-title": "Nature"
    },
    {
      "key": "2021122214330102500_bib6",
      "doi-asserted-by": "crossref",
      "first-page": "730",
      "DOI": "10.1038/nm0797-730",
      "article-title": "Human acute leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell",
      "volume": "3",
      "author": "Bonnet",
      "year": "1997",
      "journal-title": "Nat Med"
    },
    {
      "key": "2021122214330102500_bib7",
      "doi-asserted-by": "crossref",
      "first-page": "3983",
      "DOI": "10.1073/pnas.0530291100",
      "article-title": "Prospective identification of tumorigenic breast cancer cells",
      "volume": "100",
      "author": "Al-Hajj",
      "year": "2003",
      "journal-title": "Proc Natl Acad Sci U S A"
    },
    {
      "key": "2021122214330102500_bib8",
      "doi-asserted-by": "crossref",
      "first-page": "781",
      "DOI": "10.1073/pnas.0307618100",
      "article-title": "Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line",
      "volume": "101",
      "author": "Kondo",
      "year": "2004",
      "journal-title": "Proc Natl Acad Sci U S A"
    },
    {
      "key": "2021122214330102500_bib9",
      "doi-asserted-by": "crossref",
      "first-page": "14228",
      "DOI": "10.1073/pnas.0400067101",
      "article-title": "A distinct \u201cside population\u201d of cells with high drug efflux capacity in human tumor cells",
      "volume": "101",
      "author": "Hirschmann-Jax",
      "year": "2004",
      "journal-title": "Proc Natl Acad Sci U S A"
    },
    {
      "key": "2021122214330102500_bib10",
      "doi-asserted-by": "crossref",
      "first-page": "15178",
      "DOI": "10.1073/pnas.2036535100",
      "article-title": "Cancerous stem cells can arise from pediatric brain tumors",
      "volume": "100",
      "author": "Hemmati",
      "year": "2003",
      "journal-title": "Proc Natl Acad Sci U S A"
    },
    {
      "key": "2021122214330102500_bib11",
      "doi-asserted-by": "crossref",
      "first-page": "9392",
      "DOI": "10.1038/sj.onc.1208311",
      "article-title": "Isolation of cancer stem cells from adult glioblastoma multiform",
      "volume": "23",
      "author": "Yuan",
      "year": "2004",
      "journal-title": "Oncogene"
    },
    {
      "key": "2021122214330102500_bib12",
      "doi-asserted-by": "crossref",
      "first-page": "396",
      "DOI": "10.1038/nature03128",
      "article-title": "Identification of human brain tumour initiating cells",
      "volume": "432",
      "author": "Singh",
      "year": "2004",
      "journal-title": "Nature"
    },
    {
      "key": "2021122214330102500_bib13",
      "doi-asserted-by": "crossref",
      "first-page": "1337",
      "DOI": "10.1038/nm1297-1337",
      "article-title": "Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species",
      "volume": "3",
      "author": "Goodell",
      "year": "1997",
      "journal-title": "Nat Med"
    },
    {
      "key": "2021122214330102500_bib14",
      "doi-asserted-by": "crossref",
      "first-page": "399",
      "DOI": "10.1016/j.jhep.2004.05.015",
      "article-title": "A gene-expression signature can quantify the degree of rat hepatic fibrosis",
      "volume": "41",
      "author": "Utsunomiya",
      "year": "2004",
      "journal-title": "J Hepatol"
    },
    {
      "key": "2021122214330102500_bib15",
      "doi-asserted-by": "crossref",
      "first-page": "401",
      "DOI": "10.1158/0008-5472.401.65.2",
      "article-title": "Global analysis of altered gene-expressions during the process of esophageal squamous cell carcinogenesis in the rat: A study combined with a laser microdissection and a cDNA microarray",
      "volume": "65",
      "author": "Nishida",
      "year": "2005",
      "journal-title": "Cancer Res"
    },
    {
      "key": "2021122214330102500_bib16",
      "doi-asserted-by": "crossref",
      "first-page": "365",
      "DOI": "10.1038/ng1201-365",
      "article-title": "Minimum information about a microarray experiment (MIAME)-toward standards for microarray data",
      "volume": "29",
      "author": "Brazma",
      "year": "2001",
      "journal-title": "Nat Genet"
    },
    {
      "key": "2021122214330102500_bib17",
      "doi-asserted-by": "crossref",
      "first-page": "1230",
      "DOI": "10.1053/jhep.2000.20349",
      "article-title": "Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver",
      "volume": "32",
      "author": "Suzuki",
      "year": "2000",
      "journal-title": "Hepatology"
    },
    {
      "key": "2021122214330102500_bib18",
      "first-page": "5276",
      "article-title": "Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: Clinical correlation for cisplatin resistance of ovarian carcinoma",
      "volume": "55",
      "author": "Andreotti",
      "year": "1995",
      "journal-title": "Cancer Res"
    },
    {
      "key": "2021122214330102500_bib19",
      "doi-asserted-by": "crossref",
      "first-page": "476",
      "DOI": "10.1002/hep.510230312",
      "article-title": "Identification of bipotential progenitor cells in human liver development",
      "volume": "23",
      "author": "Haruna",
      "year": "1996",
      "journal-title": "Hepatology"
    },
    {
      "key": "2021122214330102500_bib20",
      "doi-asserted-by": "crossref",
      "first-page": "1147",
      "DOI": "10.1053/j.gastro.2004.01.002",
      "article-title": "Origin and characterization of a human bipotent liver progenitor cell line",
      "volume": "126",
      "author": "Parent",
      "year": "2004",
      "journal-title": "Gastroenterology"
    },
    {
      "key": "2021122214330102500_bib21",
      "doi-asserted-by": "crossref",
      "first-page": "3987",
      "DOI": "10.1158/0008-5472.CAN-04-0424",
      "article-title": "A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells",
      "volume": "64",
      "author": "Duxbury",
      "year": "2004",
      "journal-title": "Cancer Res"
    },
    {
      "key": "2021122214330102500_bib22",
      "doi-asserted-by": "crossref",
      "first-page": "275",
      "DOI": "10.1038/nrc1590",
      "article-title": "Tumour stem cells and drug resistance",
      "author": "Dean",
      "year": "2005",
      "journal-title": "Nat Rev Cancer"
    },
    {
      "key": "2021122214330102500_bib23",
      "doi-asserted-by": "crossref",
      "first-page": "3029",
      "DOI": "10.1093/hmg/ddh331",
      "article-title": "Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839)",
      "volume": "13",
      "author": "Kakiuchi",
      "year": "2004",
      "journal-title": "Hum Mol Genet"
    },
    {
      "key": "2021122214330102500_bib24",
      "doi-asserted-by": "crossref",
      "first-page": "465",
      "DOI": "10.1038/sj.onc.1207036",
      "article-title": "CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability of pancreatic adenocarcinoma cells",
      "volume": "23",
      "author": "Duxbury",
      "year": "2004",
      "journal-title": "Oncogene"
    },
    {
      "key": "2021122214330102500_bib25",
      "doi-asserted-by": "crossref",
      "first-page": "3579",
      "DOI": "10.1101/gad.12.22.3579",
      "article-title": "GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo",
      "volume": "12",
      "author": "Morrisey",
      "year": "1998",
      "journal-title": "Genes Dev"
    },
    {
      "key": "2021122214330102500_bib26",
      "doi-asserted-by": "crossref",
      "first-page": "254",
      "DOI": "10.1046/j.1432-0436.2001.680413.x",
      "article-title": "Genomic expression analysis implicates Wnt signaling pathway and extracellular matrix alterations in hepatic specification and differentiation of murine hepatic stem cells",
      "volume": "68",
      "author": "Plescia",
      "year": "2001",
      "journal-title": "Differentiation"
    },
    {
      "key": "2021122214330102500_bib27",
      "doi-asserted-by": "crossref",
      "first-page": "2622",
      "DOI": "10.1128/MCB.25.7.2622-2631.2005",
      "article-title": "GATA6 is essential for embryonic development of the liver but dispensable for early heart formation",
      "volume": "25",
      "author": "Zhao",
      "year": "2005",
      "journal-title": "Mol Cell Biol"
    },
    {
      "key": "2021122214330102500_bib28",
      "doi-asserted-by": "crossref",
      "first-page": "131",
      "DOI": "10.1016/S0012-1606(02)00026-X",
      "article-title": "Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6",
      "volume": "254",
      "author": "Nemer",
      "year": "2003",
      "journal-title": "Dev Biol"
    },
    {
      "key": "2021122214330102500_bib29",
      "doi-asserted-by": "crossref",
      "first-page": "48063",
      "DOI": "10.1074/jbc.M406467200",
      "article-title": "Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling",
      "volume": "279",
      "author": "Paling",
      "year": "2004",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2021122214330102500_bib30",
      "doi-asserted-by": "crossref",
      "first-page": "298",
      "DOI": "10.1038/sj.onc.1206483",
      "article-title": "Association of vimentin overexpression and hepatocellular carcinoma metastasis",
      "volume": "23",
      "author": "Hu",
      "year": "2004",
      "journal-title": "Oncogene"
    }
  ],
  "container-title": "Stem Cells",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1634%2Fstemcells.2005-0282",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1634/stemcells.2005-0282",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/full-xml/10.1634/stemcells.2005-0282",
      "content-type": "application/xml",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://academic.oup.com/stmcls/article-pdf/24/3/506/41878671/stmcls_24_3_506.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://academic.oup.com/stmcls/article-pdf/24/3/506/41878671/stmcls_24_3_506.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        5,
        5
      ]
    ],
    "date-time": "2023-05-05T06:07:56Z",
    "timestamp": 1683266876000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://academic.oup.com/stmcls/article/24/3/506-513/6415886"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2005,
        10,
        20
      ]
    ]
  },
  "references-count": 30,
  "journal-issue": {
    "issue": "3",
    "published-online": {
      "date-parts": [
        [
          2005,
          10,
          20
        ]
      ]
    },
    "published-print": {
      "date-parts": [
        [
          2006,
          3,
          1
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1634/stemcells.2005-0282",
  "relation": {},
  "ISSN": [
    "1066-5099",
    "1549-4918"
  ],
  "subject": [],
  "published-other": {
    "date-parts": [
      [
        2006,
        3,
        1
      ]
    ]
  },
  "published": {
    "date-parts": [
      [
        2005,
        10,
        20
      ]
    ]
  }
}