1 Ocak 2021 Dergi makalesi Açık Erişim

Ozcan, Selahattin C.; Mutlu, Aydan; Altunok, Tugba H.; Gurpinar, Yunus; Sarioglu, Aybike; Guler, Sabire; Muchut, Robertino J.; Iglesias, Alberto A.; Celikler, Serap; Campbell, Paul M.; Yalcin, Abdullah

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/231380</identifier>
  <creators>
    <creator>
      <creatorName>Ozcan, Selahattin C.</creatorName>
      <givenName>Selahattin C.</givenName>
      <familyName>Ozcan</familyName>
      <affiliation>Koc Univ, Res Ctr Translat Med KUTTAM, TR-34450 Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Mutlu, Aydan</creatorName>
      <givenName>Aydan</givenName>
      <familyName>Mutlu</familyName>
      <affiliation>Bursa Uludag Univ, Sch Arts &amp; Sci, Dept Gen Biol, TR-16059 Bursa, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Altunok, Tugba H.</creatorName>
      <givenName>Tugba H.</givenName>
      <familyName>Altunok</familyName>
      <affiliation>Bursa Uludag Univ, Sch Vet Med, Dept Biochem, Blok A, TR-16059 Bursa, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Gurpinar, Yunus</creatorName>
      <givenName>Yunus</givenName>
      <familyName>Gurpinar</familyName>
      <affiliation>Bursa Uludag Univ, Sch Vet Med, Dept Biochem, Blok A, TR-16059 Bursa, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Sarioglu, Aybike</creatorName>
      <givenName>Aybike</givenName>
      <familyName>Sarioglu</familyName>
      <affiliation>Bursa Uludag Univ, Sch Vet Med, Dept Biochem, Blok A, TR-16059 Bursa, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Guler, Sabire</creatorName>
      <givenName>Sabire</givenName>
      <familyName>Guler</familyName>
      <affiliation>Bursa Uludag Univ, Sch Vet Med, Dept Histol &amp; Embryol, TR-16059 Bursa, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Muchut, Robertino J.</creatorName>
      <givenName>Robertino J.</givenName>
      <familyName>Muchut</familyName>
      <affiliation>Natl Univ Littoral, Coastal Agrobiotechnol Inst, Dept Mol Enzymol, RA-3000 Santa Fe, Argentina</affiliation>
    </creator>
    <creator>
      <creatorName>Iglesias, Alberto A.</creatorName>
      <givenName>Alberto A.</givenName>
      <familyName>Iglesias</familyName>
      <affiliation>Natl Univ Littoral, Coastal Agrobiotechnol Inst, Dept Mol Enzymol, RA-3000 Santa Fe, Argentina</affiliation>
    </creator>
    <creator>
      <creatorName>Celikler, Serap</creatorName>
      <givenName>Serap</givenName>
      <familyName>Celikler</familyName>
      <affiliation>Bursa Uludag Univ, Sch Arts &amp; Sci, Dept Gen Biol, TR-16059 Bursa, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Campbell, Paul M.</creatorName>
      <givenName>Paul M.</givenName>
      <familyName>Campbell</familyName>
      <affiliation>Fox Chase Canc Ctr, Marvin &amp; Concetta Greenberg Pancreat Canc Inst, Canc Signaling &amp; Epigenet Program, Philadelphia, PA 19111 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Yalcin, Abdullah</creatorName>
      <givenName>Abdullah</givenName>
      <familyName>Yalcin</familyName>
      <affiliation>Bursa Uludag Univ, Sch Vet Med, Dept Biochem, Blok A, TR-16059 Bursa, Turkey</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Simultaneous Inhibition Of Pfkfb3 And Gls1 Selectively Kills Kras Transformed Pancreatic Cells</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2021</publicationYear>
  <dates>
    <date dateType="Issued">2021-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/231380</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.bbrc.2021.07.070</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">Activating mutations of the oncogenic KRAS in pancreatic ductal adenocarcinoma (PDAC) are associated with an aberrant metabolic phenotype that may be therapeutically exploited. Increased glutamine utilization via glutaminase-1 (GLS1) is one such feature of the activated KRAS signaling that is essential to cell survival and proliferation; however, metabolic plasticity of PDAC cells allow them to adapt to GLS1 inhibition via various mechanisms including activation of glycolysis, suggesting a requirement for combinatorial anti-metabolic approaches to combat PDAC. We investigated whether targeting the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) in combination with GLS1 can selectively prevent the growth of KRAS-transformed cells. We show that KRAStransformation of pancreatic duct cells robustly sensitizes them to the dual targeting of GLS1 and PFKFB3. We also report that this sensitivity is preserved in the PDAC cell line PANC-1 which harbors an activating KRAS mutation. We then demonstrate that GLS1 inhibition reduced fructose-2,6-bisphosphate levels, the product of PFKFB3, whereas PFKFB3 inhibition increased glutamine consumption, and these effects were augmented by the co-inhibition of GLS1 and PFKFB3, suggesting a reciprocal regulation between PFKFB3 and GLS1. In conclusion, this study identifies a novel mutant KRAS-induced metabolic vulnerability that may be targeted via combinatorial inhibition of GLS1 and PFKFB3 to suppress PDAC cell growth. (c) 2021 Published by Elsevier Inc.</description>
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