ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer
Identifieur interne : 000491 ( Main/Exploration ); précédent : 000490; suivant : 000492ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer
Auteurs : Gaurav Pandey ; Nicholas Borcherding [États-Unis] ; Ryan Kolb ; Paige Kluz ; Wei Li ; Sonia Sugg ; Jun Zhang ; Dazhi A. Lai ; Weizhou ZhangSource :
- Cancers [ 2072-6694 ] ; 2019.
Abstract
Among all breast cancer types, basal-like breast cancer (BLBC) represents an aggressive subtype that lacks targeted therapy. We and others have found that receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in BLBC and other types of cancer and that ROR1 is significantly correlated with patient prognosis. In addition, using primary patient-derived xenografts (PDXs) and
Url:
DOI: 10.3390/cancers11050718
PubMed: 31137681
PubMed Central: 6562526
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer</title><author><name sortKey="Pandey, Gaurav" sort="Pandey, Gaurav" uniqKey="Pandey G" first="Gaurav" last="Pandey">Gaurav Pandey</name><affiliation><nlm:aff id="af1-cancers-11-00718">Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>gpandey@wustl.edu</email> (G.P.);<email>nicholas-borcherding@uiowa.edu</email> (N.B.);<email>paige-kluz@uiowa.edu</email> (P.K.)</nlm:aff></affiliation></author><author><name sortKey="Borcherding, Nicholas" sort="Borcherding, Nicholas" uniqKey="Borcherding N" first="Nicholas" last="Borcherding">Nicholas Borcherding</name><affiliation><nlm:aff id="af1-cancers-11-00718">Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>gpandey@wustl.edu</email> (G.P.);<email>nicholas-borcherding@uiowa.edu</email> (N.B.);<email>paige-kluz@uiowa.edu</email> (P.K.)</nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="af2-cancers-11-00718">Cancer Biology Graduate Program, College of Medicine, University of Iowa, Iowa City, IA 52242, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cancer Biology Graduate Program, College of Medicine, University of Iowa, Iowa City, IA 52242</wicri:regionArea><orgName type="university">Université de l'Iowa</orgName><placeName><settlement type="city">Iowa City</settlement><region type="state">Iowa</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af3-cancers-11-00718">Medical Scientist Training Program, College of Medicine, University of Iowa, Iowa City, IA 52242, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Scientist Training Program, College of Medicine, University of Iowa, Iowa City, IA 52242</wicri:regionArea><orgName type="university">Université de l'Iowa</orgName><placeName><settlement type="city">Iowa City</settlement><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Kolb, Ryan" sort="Kolb, Ryan" uniqKey="Kolb R" first="Ryan" last="Kolb">Ryan Kolb</name><affiliation><nlm:aff id="af4-cancers-11-00718">Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA;<email>ryankolb@ufl.edu</email> (R.K.);<email>weili1978@gmail.com</email> (W.L.)</nlm:aff></affiliation></author><author><name sortKey="Kluz, Paige" sort="Kluz, Paige" uniqKey="Kluz P" first="Paige" last="Kluz">Paige Kluz</name><affiliation><nlm:aff id="af1-cancers-11-00718">Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>gpandey@wustl.edu</email> (G.P.);<email>nicholas-borcherding@uiowa.edu</email> (N.B.);<email>paige-kluz@uiowa.edu</email> (P.K.)</nlm:aff></affiliation></author><author><name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name><affiliation><nlm:aff id="af4-cancers-11-00718">Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA;<email>ryankolb@ufl.edu</email> (R.K.);<email>weili1978@gmail.com</email> (W.L.)</nlm:aff></affiliation></author><author><name sortKey="Sugg, Sonia" sort="Sugg, Sonia" uniqKey="Sugg S" first="Sonia" last="Sugg">Sonia Sugg</name><affiliation><nlm:aff id="af5-cancers-11-00718">Department of Surgery, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>sonia-sugg@uiowa.edu</email></nlm:aff></affiliation></author><author><name sortKey="Zhang, Jun" sort="Zhang, Jun" uniqKey="Zhang J" first="Jun" last="Zhang">Jun Zhang</name><affiliation><nlm:aff id="af6-cancers-11-00718">Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>jun-zhang-1@uiowa.edu</email></nlm:aff></affiliation></author><author><name sortKey="Lai, Dazhi A" sort="Lai, Dazhi A" uniqKey="Lai D" first="Dazhi A." last="Lai">Dazhi A. Lai</name><affiliation><nlm:aff id="af7-cancers-11-00718">Speed Biosystems, Gaithersburg, MD 20878, USA;<email>alex.lai@speedbiosystems.com</email></nlm:aff></affiliation></author><author><name sortKey="Zhang, Weizhou" sort="Zhang, Weizhou" uniqKey="Zhang W" first="Weizhou" last="Zhang">Weizhou Zhang</name><affiliation><nlm:aff id="af4-cancers-11-00718">Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA;<email>ryankolb@ufl.edu</email> (R.K.);<email>weili1978@gmail.com</email> (W.L.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31137681</idno><idno type="pmc">6562526</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562526</idno><idno type="RBID">PMC:6562526</idno><idno type="doi">10.3390/cancers11050718</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000451</idno><idno type="wicri:explorRef" wicri:stream="Pmc" 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of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>gpandey@wustl.edu</email> (G.P.);<email>nicholas-borcherding@uiowa.edu</email> (N.B.);<email>paige-kluz@uiowa.edu</email> (P.K.)</nlm:aff></affiliation></author><author><name sortKey="Borcherding, Nicholas" sort="Borcherding, Nicholas" uniqKey="Borcherding N" first="Nicholas" last="Borcherding">Nicholas Borcherding</name><affiliation><nlm:aff id="af1-cancers-11-00718">Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>gpandey@wustl.edu</email> (G.P.);<email>nicholas-borcherding@uiowa.edu</email> (N.B.);<email>paige-kluz@uiowa.edu</email> (P.K.)</nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="af2-cancers-11-00718">Cancer Biology Graduate Program, College of Medicine, University of Iowa, Iowa City, IA 52242, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cancer Biology Graduate Program, College of Medicine, University of Iowa, Iowa City, IA 52242</wicri:regionArea><orgName type="university">Université de l'Iowa</orgName><placeName><settlement type="city">Iowa City</settlement><region type="state">Iowa</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af3-cancers-11-00718">Medical Scientist Training Program, College of Medicine, University of Iowa, Iowa City, IA 52242, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Scientist Training Program, College of Medicine, University of Iowa, Iowa City, IA 52242</wicri:regionArea><orgName type="university">Université de l'Iowa</orgName><placeName><settlement type="city">Iowa City</settlement><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Kolb, Ryan" sort="Kolb, Ryan" uniqKey="Kolb R" first="Ryan" last="Kolb">Ryan Kolb</name><affiliation><nlm:aff id="af4-cancers-11-00718">Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA;<email>ryankolb@ufl.edu</email> (R.K.);<email>weili1978@gmail.com</email> (W.L.)</nlm:aff></affiliation></author><author><name sortKey="Kluz, Paige" sort="Kluz, Paige" uniqKey="Kluz P" first="Paige" last="Kluz">Paige Kluz</name><affiliation><nlm:aff id="af1-cancers-11-00718">Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>gpandey@wustl.edu</email> (G.P.);<email>nicholas-borcherding@uiowa.edu</email> (N.B.);<email>paige-kluz@uiowa.edu</email> (P.K.)</nlm:aff></affiliation></author><author><name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name><affiliation><nlm:aff id="af4-cancers-11-00718">Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA;<email>ryankolb@ufl.edu</email> (R.K.);<email>weili1978@gmail.com</email> (W.L.)</nlm:aff></affiliation></author><author><name sortKey="Sugg, Sonia" sort="Sugg, Sonia" uniqKey="Sugg S" first="Sonia" last="Sugg">Sonia Sugg</name><affiliation><nlm:aff id="af5-cancers-11-00718">Department of Surgery, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>sonia-sugg@uiowa.edu</email></nlm:aff></affiliation></author><author><name sortKey="Zhang, Jun" sort="Zhang, Jun" uniqKey="Zhang J" first="Jun" last="Zhang">Jun Zhang</name><affiliation><nlm:aff id="af6-cancers-11-00718">Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA 52242, USA;<email>jun-zhang-1@uiowa.edu</email></nlm:aff></affiliation></author><author><name sortKey="Lai, Dazhi A" sort="Lai, Dazhi A" uniqKey="Lai D" first="Dazhi A." last="Lai">Dazhi A. Lai</name><affiliation><nlm:aff id="af7-cancers-11-00718">Speed Biosystems, Gaithersburg, MD 20878, USA;<email>alex.lai@speedbiosystems.com</email></nlm:aff></affiliation></author><author><name sortKey="Zhang, Weizhou" sort="Zhang, Weizhou" uniqKey="Zhang W" first="Weizhou" last="Zhang">Weizhou Zhang</name><affiliation><nlm:aff id="af4-cancers-11-00718">Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA;<email>ryankolb@ufl.edu</email> (R.K.);<email>weili1978@gmail.com</email> (W.L.)</nlm:aff></affiliation></author></analytic><series><title level="j">Cancers</title><idno type="eISSN">2072-6694</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Among all breast cancer types, basal-like breast cancer (BLBC) represents an aggressive subtype that lacks targeted therapy. We and others have found that receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in BLBC and other types of cancer and that ROR1 is significantly correlated with patient prognosis. In addition, using primary patient-derived xenografts (PDXs) and <italic>ROR1</italic>-knockout BLBC cells, we found that ROR1<sup>+</sup> cells form tumors in immunodeficient mice. We developed an anti-ROR1 immunotoxin and found that targeting ROR1 significantly kills ROR1<sup>+</sup> cancer cells and slows down tumor growth in ROR1<sup>+</sup> xenografts. Our bioinformatics analysis revealed that ROR1 expression is commonly associated with the activation of FGFR-mediated signaling pathway. Further biochemical analysis confirmed that ROR1 stabilized FGFR expression at the posttranslational level by preventing its degradation. CRISPR/Cas9-mediated <italic>ROR1</italic> knockout significantly reduced cancer cell invasion at cellular levels by lowering FGFR protein and consequent inactivation of AKT. Our results identified a novel signaling regulation from ROR1 to FGFR and further confirm that ROR1 is a potential therapeutic target for ROR1<sup>+</sup> BLBC cells.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bray, F" uniqKey="Bray F">F. Bray</name></author><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J. Ferlay</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I. Soerjomataram</name></author><author><name sortKey="Siegel, R L" uniqKey="Siegel R">R.L. Siegel</name></author><author><name sortKey="Torre, L A" uniqKey="Torre L">L.A. Torre</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal A">A. 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Zhang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Iowa</li></region><settlement><li>Iowa City</li></settlement><orgName><li>Université de l'Iowa</li></orgName></list><tree><noCountry><name sortKey="Kluz, Paige" sort="Kluz, Paige" uniqKey="Kluz P" first="Paige" last="Kluz">Paige Kluz</name><name sortKey="Kolb, Ryan" sort="Kolb, Ryan" uniqKey="Kolb R" first="Ryan" last="Kolb">Ryan Kolb</name><name sortKey="Lai, Dazhi A" sort="Lai, Dazhi A" uniqKey="Lai D" first="Dazhi A." last="Lai">Dazhi A. Lai</name><name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name><name sortKey="Pandey, Gaurav" sort="Pandey, Gaurav" uniqKey="Pandey G" first="Gaurav" last="Pandey">Gaurav Pandey</name><name sortKey="Sugg, Sonia" sort="Sugg, Sonia" uniqKey="Sugg S" first="Sonia" last="Sugg">Sonia Sugg</name><name sortKey="Zhang, Jun" sort="Zhang, Jun" uniqKey="Zhang J" first="Jun" last="Zhang">Jun Zhang</name><name sortKey="Zhang, Weizhou" sort="Zhang, Weizhou" uniqKey="Zhang W" first="Weizhou" last="Zhang">Weizhou Zhang</name></noCountry><country name="États-Unis"><region name="Iowa"><name sortKey="Borcherding, Nicholas" sort="Borcherding, Nicholas" uniqKey="Borcherding N" first="Nicholas" last="Borcherding">Nicholas Borcherding</name></region><name sortKey="Borcherding, Nicholas" sort="Borcherding, Nicholas" uniqKey="Borcherding N" first="Nicholas" last="Borcherding">Nicholas Borcherding</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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