DOI: 10.1158/1078-0432.ccr-08-0436. Human Mena+11a Isoform Serves as a Marker of Epithelial Phenotype and Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Pancreatic Cancer Cell Lines

Human Mena+11a Isoform Serves as a Marker of Epithelial Phenotype and Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Pancreatic Cancer Cell Lines

10.1158/1078-0432.ccr-08-0436

Crossref journal-article

American Association for Cancer Research (AACR)

Clinical Cancer Research (1086)

Abstract

Abstract Purpose: hMena, member of the enabled/vasodilator-stimulated phosphoprotein family, is a cytoskeletal protein that is involved in the regulation of cell motility and adhesion. The aim of this study was to determine whether or not the expression of hMena isoforms correlated with sensitivity to EGFR tyrosine kinase inhibitors and could serve as markers with potential clinical use. Experimental Design: Human pancreatic ductal adenocarcinoma cell lines were characterized for in vitro sensitivity to erlotinib, expression of HER family receptors, markers of epithelial to mesenchymal transition, and expression of hMena and its isoform hMena+11a. The effects of epidermal growth factor (EGF) and erlotinib on hMena expression as well as the effect of hMena knockdown on cell proliferation were also evaluated. Results: hMena was detected in all of the pancreatic tumor cell lines tested as well as in the majority of the human tumor samples [primary (92%) and metastatic (86%)]. Intriguingly, in vitro hMena+11a isoform was specifically associated with an epithelial phenotype, EGFR dependency, and sensitivity to erlotinib. In epithelial BxPC3 cells, epidermal growth factor up-regulated hMena/hMena+11a and erlotinib down-regulated expression. hMena knockdown reduced cell proliferation and mitogen-activated protein kinase and AKT activation in BxPC3 cells, and promoted the growth inhibitory effects of erlotinib. Conclusions: Collectively, our data indicate that the hMena+11a isoform is associated with an epithelial phenotype and identifies EGFR-dependent cell lines that are sensitive to the EGFR inhibitor erlotinib. The availability of anti-hMena+11a–specific probes may offer a new tool in pancreatic cancer management if these results can be verified prospectively in cancer patients.

Bibliography

Pino, M. S., Balsamo, M., Di Modugno, F., Mottolese, M., Alessio, M., Melucci, E., Milella, M., McConkey, D. J., Philippar, U., Gertler, F. B., Natali, P. G., & NisticoÌ, P. (2008). Human Mena+11a Isoform Serves as a Marker of Epithelial Phenotype and Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Pancreatic Cancer Cell Lines. Clinical Cancer Research, 14(15), 4943â4950.

Authors 12

Maria S. Pino (first)
Michele Balsamo (additional)
Francesca Di Modugno (additional)
Marcella Mottolese (additional)
Massimo Alessio (additional)
Elisa Melucci (additional)
Michele Milella (additional)
David J. McConkey (additional)
Ulrike Philippar (additional)
Frank B. Gertler (additional)
Pier Giorgio Natali (additional)
Paola Nisticò (additional)

References 50 Referenced 53

Dates

Type	When
Created	17 years ago (Aug. 1, 2008, 12:58 p.m.)
Deposited	3 years, 2 months ago (June 10, 2022, 10:42 p.m.)
Indexed	1 year ago (Aug. 23, 2024, 3:52 a.m.)
Issued	17 years ago (Aug. 1, 2008)
Published	17 years ago (Aug. 1, 2008)
Published Online	17 years ago (Aug. 1, 2008)
Published Print	17 years ago (Aug. 1, 2008)

Funders 0

None

BibTeX

@article{Pino_2008, title={Human Mena+11a Isoform Serves as a Marker of Epithelial Phenotype and Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Pancreatic Cancer Cell Lines}, volume={14}, ISSN={1557-3265}, url={http://dx.doi.org/10.1158/1078-0432.ccr-08-0436}, DOI={10.1158/1078-0432.ccr-08-0436}, number={15}, journal={Clinical Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Pino, Maria S. and Balsamo, Michele and Di Modugno, Francesca and Mottolese, Marcella and Alessio, Massimo and Melucci, Elisa and Milella, Michele and McConkey, David J. and Philippar, Ulrike and Gertler, Frank B. and Natali, Pier Giorgio and Nisticò, Paola}, year={2008}, month=aug, pages={4943–4950} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        8,
        23
      ]
    ],
    "date-time": "2024-08-23T07:52:35Z",
    "timestamp": 1724399555655
  },
  "reference-count": 50,
  "publisher": "American Association for Cancer Research (AACR)",
  "issue": "15",
  "content-domain": {
    "domain": [
      "aacrjournals.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2008,
        8,
        1
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>Purpose: hMena, member of the enabled/vasodilator-stimulated phosphoprotein family, is a cytoskeletal protein that is involved in the regulation of cell motility and adhesion. The aim of this study was to determine whether or not the expression of hMena isoforms correlated with sensitivity to EGFR tyrosine kinase inhibitors and could serve as markers with potential clinical use.</jats:p>\n               <jats:p>Experimental Design: Human pancreatic ductal adenocarcinoma cell lines were characterized for in vitro sensitivity to erlotinib, expression of HER family receptors, markers of epithelial to mesenchymal transition, and expression of hMena and its isoform hMena+11a. The effects of epidermal growth factor (EGF) and erlotinib on hMena expression as well as the effect of hMena knockdown on cell proliferation were also evaluated.</jats:p>\n               <jats:p>Results: hMena was detected in all of the pancreatic tumor cell lines tested as well as in the majority of the human tumor samples [primary (92%) and metastatic (86%)]. Intriguingly, in vitro hMena+11a isoform was specifically associated with an epithelial phenotype, EGFR dependency, and sensitivity to erlotinib. In epithelial BxPC3 cells, epidermal growth factor up-regulated hMena/hMena+11a and erlotinib down-regulated expression. hMena knockdown reduced cell proliferation and mitogen-activated protein kinase and AKT activation in BxPC3 cells, and promoted the growth inhibitory effects of erlotinib.</jats:p>\n               <jats:p>Conclusions: Collectively, our data indicate that the hMena+11a isoform is associated with an epithelial phenotype and identifies EGFR-dependent cell lines that are sensitive to the EGFR inhibitor erlotinib. The availability of anti-hMena+11a\u2013specific probes may offer a new tool in pancreatic cancer management if these results can be verified prospectively in cancer patients.</jats:p>",
  "DOI": "10.1158/1078-0432.ccr-08-0436",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2008,
        8,
        1
      ]
    ],
    "date-time": "2008-08-01T16:58:46Z",
    "timestamp": 1217609926000
  },
  "page": "4943-4950",
  "update-policy": "http://dx.doi.org/10.1158/crossmark_policy",
  "source": "Crossref",
  "is-referenced-by-count": 53,
  "title": "Human Mena+11a Isoform Serves as a Marker of Epithelial Phenotype and Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Pancreatic Cancer Cell Lines",
  "prefix": "10.1158",
  "volume": "14",
  "author": [
    {
      "given": "Maria S.",
      "family": "Pino",
      "sequence": "first",
      "affiliation": [
        {
          "name": "1Division of Medical Oncology, Laboratories of"
        }
      ]
    },
    {
      "given": "Michele",
      "family": "Balsamo",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "2Immunology,"
        },
        {
          "name": "7David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, Massachusetts"
        }
      ]
    },
    {
      "given": "Francesca",
      "family": "Di Modugno",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "3Experimental Chemotherapy, and"
        }
      ]
    },
    {
      "given": "Marcella",
      "family": "Mottolese",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "4Pathology, Regina Elena National Cancer Institute, Rome, Italy;"
        }
      ]
    },
    {
      "given": "Massimo",
      "family": "Alessio",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "5Proteome Biochemistry, Dibit, San Raffaele Scientific Institute, Milan, Italy;"
        }
      ]
    },
    {
      "given": "Elisa",
      "family": "Melucci",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "4Pathology, Regina Elena National Cancer Institute, Rome, Italy;"
        }
      ]
    },
    {
      "given": "Michele",
      "family": "Milella",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "1Division of Medical Oncology, Laboratories of"
        }
      ]
    },
    {
      "given": "David J.",
      "family": "McConkey",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "6Department of Cancer Biology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas; and"
        }
      ]
    },
    {
      "given": "Ulrike",
      "family": "Philippar",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "7David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, Massachusetts"
        }
      ]
    },
    {
      "given": "Frank B.",
      "family": "Gertler",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "7David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, Massachusetts"
        }
      ]
    },
    {
      "given": "Pier Giorgio",
      "family": "Natali",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "2Immunology,"
        }
      ]
    },
    {
      "given": "Paola",
      "family": "Nistico\u0300",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "2Immunology,"
        }
      ]
    }
  ],
  "member": "1086",
  "published-online": {
    "date-parts": [
      [
        2008,
        8,
        1
      ]
    ]
  },
  "reference": [
    {
      "key": "2022061021365652600_B1",
      "doi-asserted-by": "crossref",
      "unstructured": "Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer Statistics, 2007. CA Cancer J Clin\u20082007;57:43\u201366.",
      "DOI": "10.3322/canjclin.57.1.43"
    },
    {
      "key": "2022061021365652600_B2",
      "doi-asserted-by": "crossref",
      "unstructured": "Burris H III, Moore M, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol\u20081997;15:2403\u201313.",
      "DOI": "10.1200/JCO.1997.15.6.2403"
    },
    {
      "key": "2022061021365652600_B3",
      "doi-asserted-by": "crossref",
      "unstructured": "Heinemann V, Quietzsch D, Gieseler F, et al. Randomized phase iii trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol\u20082006;24:3946\u201352.",
      "DOI": "10.1200/JCO.2005.05.1490"
    },
    {
      "key": "2022061021365652600_B4",
      "doi-asserted-by": "crossref",
      "unstructured": "Louvet C, Labianca R, Hammel P, et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol\u20082005;23:3509\u201316.",
      "DOI": "10.1200/JCO.2005.06.023"
    },
    {
      "key": "2022061021365652600_B5",
      "doi-asserted-by": "crossref",
      "unstructured": "Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol\u20082007;25:1960\u20136.",
      "DOI": "10.1200/JCO.2006.07.9525"
    },
    {
      "key": "2022061021365652600_B6",
      "doi-asserted-by": "crossref",
      "unstructured": "Oettle H, Richards D, Ramanathan RK, et al. A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol\u20082005;16:1639\u201345.",
      "DOI": "10.1093/annonc/mdi309"
    },
    {
      "key": "2022061021365652600_B7",
      "doi-asserted-by": "crossref",
      "unstructured": "Rocha Lima CM, Green MR, Rotche R, et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response Rate. J Clin Oncol\u20082004;22:3776\u201383.",
      "DOI": "10.1200/JCO.2004.12.082"
    },
    {
      "key": "2022061021365652600_B8",
      "doi-asserted-by": "crossref",
      "unstructured": "Van Cutsem E, van de Velde H, Karasek P, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol\u20082004;22:1430\u20138.",
      "DOI": "10.1200/JCO.2004.10.112"
    },
    {
      "key": "2022061021365652600_B9",
      "doi-asserted-by": "crossref",
      "unstructured": "Bria E, Milella M, Gelibter A, et al. Gemcitabine-based combinations for inoperable pancreatic cancer: Have we made real progress? Cancer\u20082007;110:525\u201333.",
      "DOI": "10.1002/cncr.22809"
    },
    {
      "key": "2022061021365652600_B10",
      "doi-asserted-by": "crossref",
      "unstructured": "Grandis J, Melhem M, Gooding W, et al. Levels of TGF-\u03b1 and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst\u20081998;90:824\u201332.",
      "DOI": "10.1093/jnci/90.11.824"
    },
    {
      "key": "2022061021365652600_B11",
      "doi-asserted-by": "crossref",
      "unstructured": "Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol\u20081995;19:183\u2013232.",
      "DOI": "10.1016/1040-8428(94)00144-I"
    },
    {
      "key": "2022061021365652600_B12",
      "doi-asserted-by": "crossref",
      "unstructured": "Kondapaka SB, Fridman R, Reddy KB. Epidermal growth factor and amphiregulin up-regulate matrix metalloproteinase-9 (MMP-9) in human breast cancer cells. Int J Cancer\u20081997;70:722\u20136.",
      "DOI": "10.1002/(SICI)1097-0215(19970317)70:6<722::AID-IJC15>3.0.CO;2-B"
    },
    {
      "key": "2022061021365652600_B13",
      "doi-asserted-by": "crossref",
      "unstructured": "Ennis BW, Lippman ME, Dickson RB. The EGF receptor system as a target for antitumor therapy. Cancer Invest\u20081991;9:553\u201362.",
      "DOI": "10.3109/07357909109018953"
    },
    {
      "key": "2022061021365652600_B14",
      "doi-asserted-by": "crossref",
      "unstructured": "Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J\u20082000;19:3159\u201367.",
      "DOI": "10.1093/emboj/19.13.3159"
    },
    {
      "key": "2022061021365652600_B15",
      "doi-asserted-by": "crossref",
      "unstructured": "Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol\u20082001;2:127\u201337.",
      "DOI": "10.1038/35052073"
    },
    {
      "key": "2022061021365652600_B16",
      "unstructured": "Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res\u20081993;13:565\u20139."
    },
    {
      "key": "2022061021365652600_B17",
      "doi-asserted-by": "crossref",
      "unstructured": "Barton CM, Hall PA, Hughes CM, Gullick WJ, Lemoine NR. Transforming growth factor \u03b1 and epidermal growth factor in human pancreatic cancer. J Pathol\u20081991;163:111\u20136.",
      "DOI": "10.1002/path.1711630206"
    },
    {
      "key": "2022061021365652600_B18",
      "doi-asserted-by": "crossref",
      "unstructured": "Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger HG. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor \u03b1. J Clin Invest\u20081992;90:1352\u201360.",
      "DOI": "10.1172/JCI116001"
    },
    {
      "key": "2022061021365652600_B19",
      "doi-asserted-by": "crossref",
      "unstructured": "Wagner M, Cao T, Lopez ME, et al. Expression of a truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatinum. Int J Cancer\u20081996;68:782\u20137.",
      "DOI": "10.1002/(SICI)1097-0215(19961211)68:6<782::AID-IJC16>3.0.CO;2-2"
    },
    {
      "key": "2022061021365652600_B20",
      "unstructured": "Moasser MM, Basso A, Averbuch SD, Rosen N. The tyrosine kinase inhibitor ZD1839 (\u201cIressa\u201d) inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res\u20082001;61:7184\u20138."
    },
    {
      "key": "2022061021365652600_B21",
      "doi-asserted-by": "crossref",
      "unstructured": "Engelman JA, Janne PA, Mermel C, et al. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines. Proc Natl Acad Sci U S A\u20082005;102:3788\u201393.",
      "DOI": "10.1073/pnas.0409773102"
    },
    {
      "key": "2022061021365652600_B22",
      "doi-asserted-by": "crossref",
      "unstructured": "Thomson S, Buck E, Petti F, et al. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res\u20082005;65:9455\u201362.",
      "DOI": "10.1158/0008-5472.CAN-05-1058"
    },
    {
      "key": "2022061021365652600_B23",
      "doi-asserted-by": "crossref",
      "unstructured": "Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med\u20082004;350:2129\u201339.",
      "DOI": "10.1056/NEJMoa040938"
    },
    {
      "key": "2022061021365652600_B24",
      "doi-asserted-by": "crossref",
      "unstructured": "Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med\u20082005;353:123\u201332.",
      "DOI": "10.1056/NEJMoa050753"
    },
    {
      "key": "2022061021365652600_B25",
      "doi-asserted-by": "crossref",
      "unstructured": "Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer-molecular and clinical predictors of outcome. N Engl J Med\u20082005;353:133\u201344.",
      "DOI": "10.1056/NEJMoa050736"
    },
    {
      "key": "2022061021365652600_B26",
      "doi-asserted-by": "crossref",
      "unstructured": "Yamaguchi H, Wyckoff J, Condeelis J. Cell migration in tumors. Curr Opin Cell Biol\u20082005;17:559\u201364.",
      "DOI": "10.1016/j.ceb.2005.08.002"
    },
    {
      "key": "2022061021365652600_B27",
      "doi-asserted-by": "crossref",
      "unstructured": "Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature\u20082007;449:557\u201363.",
      "DOI": "10.1038/nature06188"
    },
    {
      "key": "2022061021365652600_B28",
      "doi-asserted-by": "crossref",
      "unstructured": "Hay ED. The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn\u20082005;233:706\u201320.",
      "DOI": "10.1002/dvdy.20345"
    },
    {
      "key": "2022061021365652600_B29",
      "doi-asserted-by": "crossref",
      "unstructured": "Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol\u20082006;172:973\u201381.",
      "DOI": "10.1083/jcb.200601018"
    },
    {
      "key": "2022061021365652600_B30",
      "doi-asserted-by": "crossref",
      "unstructured": "Buck E, Eyzaguirre A, Barr S, et al. Loss of homotypic cell adhesion by epithelial-mesenchymal transition or mutation limits sensitivity to epidermal growth factor receptor inhibition. Mol Cancer Ther\u20082007;6:532\u201341.",
      "DOI": "10.1158/1535-7163.MCT-06-0462"
    },
    {
      "key": "2022061021365652600_B31",
      "doi-asserted-by": "crossref",
      "unstructured": "Black PC, Brown GA, Inamoto T, et al. Sensitivity to epidermal growth factor receptor inhibitor requires E-cadherin expression in urothelial carcinoma cells. Clin Cancer Res\u20082008;14:1478\u201386.",
      "DOI": "10.1158/1078-0432.CCR-07-1593"
    },
    {
      "key": "2022061021365652600_B32",
      "doi-asserted-by": "crossref",
      "unstructured": "Shrader M, Pino MS, Brown G, et al. Molecular correlates of gefitinib responsiveness in human bladder cancer cells. Mol Cancer Ther\u20082007;6:277\u201385.",
      "DOI": "10.1158/1535-7163.MCT-06-0513"
    },
    {
      "key": "2022061021365652600_B33",
      "doi-asserted-by": "crossref",
      "unstructured": "Krause M, Dent EW, Bear JE, Loureiro JJ, Gertler FB. Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Annu Rev Cell Dev Biol\u20082003;19:541\u201364.",
      "DOI": "10.1146/annurev.cellbio.19.050103.103356"
    },
    {
      "key": "2022061021365652600_B34",
      "doi-asserted-by": "crossref",
      "unstructured": "Di Modugno F, Mottolese M, Di Benedetto A, et al. The cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors. Clin Cancer Res\u20082006;12:1470\u20138.",
      "DOI": "10.1158/1078-0432.CCR-05-2027"
    },
    {
      "key": "2022061021365652600_B35",
      "doi-asserted-by": "crossref",
      "unstructured": "Di Modugno F, Bronzi G, Scanlan MJ, et al. Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8+ T-cell immune response. Int J Cancer\u20082004;109:909\u201318.",
      "DOI": "10.1002/ijc.20094"
    },
    {
      "key": "2022061021365652600_B36",
      "doi-asserted-by": "crossref",
      "unstructured": "Di Modugno F, DeMonte L, Balsamo M, et al. Molecular cloning of hMena (ENAH) and its splice variant hMena+11a: epidermal growth factor increases their expression and stimulates hMena+11a phosphorylation in breast cancer cell lines. Cancer Res\u20082007;67:2657\u201365.",
      "DOI": "10.1158/0008-5472.CAN-06-1997"
    },
    {
      "key": "2022061021365652600_B37",
      "doi-asserted-by": "crossref",
      "unstructured": "Bear JE, Loureiro JJ, Libova I, Fassler R, Wehland J, Gertler FB. Negative regulation of fibroblast motility by Ena/VASP proteins. Cell\u20082000;101:717\u201328.",
      "DOI": "10.1016/S0092-8674(00)80884-3"
    },
    {
      "key": "2022061021365652600_B38",
      "doi-asserted-by": "crossref",
      "unstructured": "Conti A, Ricchiuto P, Iannaccone S, et al. Pigment epithelium-derived factor is differentially expressed in peripheral neuropathies. Proteomics\u20082005;5:4558\u201367.",
      "DOI": "10.1002/pmic.200402088"
    },
    {
      "key": "2022061021365652600_B39",
      "doi-asserted-by": "crossref",
      "unstructured": "Petty WJ, Dragnev KH, Memoli VA, et al. Epidermal growth factor receptor tyrosine kinase inhibition represses cyclin D1 in aerodigestive tract cancers. Clin Cancer Res\u20082004;10:7547\u201354.",
      "DOI": "10.1158/1078-0432.CCR-04-1169"
    },
    {
      "key": "2022061021365652600_B40",
      "doi-asserted-by": "crossref",
      "unstructured": "Hidalgo M, Siu LL, Nemunaitis J, et al. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol\u20082001;19:3267\u201379.",
      "DOI": "10.1200/JCO.2001.19.13.3267"
    },
    {
      "key": "2022061021365652600_B41",
      "unstructured": "Janmaat ML, Kruyt FAE, Rodriguez JA, Giaccone G. Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. Clin Cancer Res\u20082003;9:2316\u201326."
    },
    {
      "key": "2022061021365652600_B42",
      "doi-asserted-by": "crossref",
      "unstructured": "Saltz LB, Meropol NJ, Loehrer PJ, Sr., Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol\u20082004;22:1201\u20138.",
      "DOI": "10.1200/JCO.2004.10.182"
    },
    {
      "key": "2022061021365652600_B43",
      "doi-asserted-by": "crossref",
      "unstructured": "Campiglio M, Locatelli A, Olgiati C, et al. Inhibition of proliferation and induction of apoptosis in breast cancer cells by the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa) is independent of EGFR expression level. J Cell Physiol\u20082004;198:259\u201368.",
      "DOI": "10.1002/jcp.10411"
    },
    {
      "key": "2022061021365652600_B44",
      "doi-asserted-by": "crossref",
      "unstructured": "Pino MS, Shrader M, Baker CH, et al. Transforming growth factor {\u03b1} expression drives constitutive epidermal growth factor receptor pathway activation and sensitivity to gefitinib (iressa) in human pancreatic cancer cell lines. Cancer Res\u20082006;66:3802\u201312.",
      "DOI": "10.1158/0008-5472.CAN-05-3753"
    },
    {
      "key": "2022061021365652600_B45",
      "doi-asserted-by": "crossref",
      "unstructured": "Katz M, Amit I, Citri A, et al. A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration. Nat Cell Biol\u20082007;9:961\u20139.",
      "DOI": "10.1038/ncb1622"
    },
    {
      "key": "2022061021365652600_B46",
      "doi-asserted-by": "crossref",
      "unstructured": "den Hartigh J, van Bergen en Henegouwen P, Verkleij A, Boonstra J. The EGF receptor is an actin-binding protein. J Cell Biol\u20081992;119:349\u201355.",
      "DOI": "10.1083/jcb.119.2.349"
    },
    {
      "key": "2022061021365652600_B47",
      "doi-asserted-by": "crossref",
      "unstructured": "Jimeno A, Tan AC, Coffa J, et al. Coordinated epidermal growth factor receptor pathway gene overexpression predicts epidermal growth factor receptor inhibitor sensitivity in pancreatic cancer. Cancer Res\u20082008;68:2841\u20139.",
      "DOI": "10.1158/0008-5472.CAN-07-5200"
    },
    {
      "key": "2022061021365652600_B48",
      "doi-asserted-by": "crossref",
      "unstructured": "Yauch RL, Januario T, Eberhard DA, et al. Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin Cancer Res\u20082005;11:8686\u201398.",
      "DOI": "10.1158/1078-0432.CCR-05-1492"
    },
    {
      "key": "2022061021365652600_B49",
      "doi-asserted-by": "crossref",
      "unstructured": "Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase iii trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol\u20082005;23:5892\u20139.",
      "DOI": "10.1200/JCO.2005.02.840"
    },
    {
      "key": "2022061021365652600_B50",
      "doi-asserted-by": "crossref",
      "unstructured": "Perrais M, Chen X, Perez-Moreno M, Gumbiner BM. E-cadherin homophilic ligation inhibits cell growth and epidermal growth factor receptor signaling independently of other cell interactions. Mol Biol Cell\u20082007;18:2013\u201325.",
      "DOI": "10.1091/mbc.e06-04-0348"
    }
  ],
  "container-title": "Clinical Cancer Research",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://aacrjournals.org/clincancerres/article-pdf/14/15/4943/1975607/4943.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://aacrjournals.org/clincancerres/article-pdf/14/15/4943/1975607/4943.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        6,
        11
      ]
    ],
    "date-time": "2022-06-11T02:42:22Z",
    "timestamp": 1654915342000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://aacrjournals.org/clincancerres/article/14/15/4943/72594/Human-Mena-11a-Isoform-Serves-as-a-Marker-of"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2008,
        8,
        1
      ]
    ]
  },
  "references-count": 50,
  "journal-issue": {
    "issue": "15",
    "published-online": {
      "date-parts": [
        [
          2008,
          8,
          1
        ]
      ]
    },
    "published-print": {
      "date-parts": [
        [
          2008,
          8,
          1
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1158/1078-0432.CCR-08-0436",
  "relation": {},
  "ISSN": [
    "1078-0432",
    "1557-3265"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2008,
        8,
        1
      ]
    ]
  }
}