Influences of TP53 and the anti-aging DDR1 receptor in controlling Raf/MEK/ERK and PI3K/Akt expression and chemotherapeutic drug sensitivity in prostate cancer cell lines.
Identifieur interne : 000105 ( Main/Exploration ); précédent : 000104; suivant : 000106Influences of TP53 and the anti-aging DDR1 receptor in controlling Raf/MEK/ERK and PI3K/Akt expression and chemotherapeutic drug sensitivity in prostate cancer cell lines.
Auteurs : William H. Chappell [États-Unis] ; Saverio Candido [Italie] ; Stephen L. Abrams [États-Unis] ; Shaw M. Akula [États-Unis] ; Linda S. Steelman [États-Unis] ; Alberto M. Martelli [Italie] ; Stefano Ratti [Italie] ; Lucio Cocco [Italie] ; Melchiorre Cervello [Italie] ; Giuseppe Montalto [Italie] ; Ferdinando Nicoletti [Italie] ; Massimo Libra [Italie] ; James A. Mccubrey [États-Unis]Source :
- Aging [ 1945-4589 ] ; 2020.
Abstract
BACKGROUND
TP53 plays critical roles in sensitivity to chemotherapy, and aging. Collagen is very important in aging. The molecular structure and biochemical properties of collagen changes during aging. The discoidin domain receptor (DDR1) is regulated in part by collagen. Elucidating the links between TP53 and DDR1 in chemosensitivity and aging could improve therapies against cancer and aging.
RESULTS
Restoration of WT-TP53 activity resulted in increased sensitivity to chemotherapeutic drugs and elevated expression of key components of the Raf/MEK/ERK, PI3K/Akt and DDR1 pathways. DDR1 could modulate the levels of Raf/MEK/ERK and PI3K/Akt pathways as well as sensitize the cells to chemotherapeutic drugs. In contrast, suppression of WT TP53 with a dominant negative (DN) TP53 gene, suppressed DDR1 protein levels and increased their chemoresistance.
CONCLUSION
Restoration of WT TP53 activity or increased expression of the anti-aging DDR1 collagen receptor can result in enhanced sensitivity to chemotherapeutic drugs. Our innovative studies indicate the important links between WT TP53 and DDR1 which can modulate Raf/MEK/ERK and PI3K/Akt signaling as well as chemosensitivity and aging.
METHODS
We investigated the roles of wild type (WT) and mutant TP53 on drug sensitivity of prostate cancer cells and the induction of Raf/MEK/ERK, PI3K/Akt and DDR1 expression and chemosensitivity.
DOI: 10.18632/aging.103377
PubMed: 32492656
PubMed Central: PMC7346063
Affiliations:
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Chappell</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Current Address: Becton, Dickinson and Company (BD), BD Diagnostics, Franklin Lakes, NJ 07417, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Current Address: Becton, Dickinson and Company (BD), BD Diagnostics, Franklin Lakes, NJ 07417</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Candido, Saverio" sort="Candido, Saverio" uniqKey="Candido S" first="Saverio" last="Candido">Saverio Candido</name><affiliation wicri:level="1"><nlm:affiliation>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation></author><author><name sortKey="Abrams, Stephen L" sort="Abrams, Stephen L" uniqKey="Abrams S" first="Stephen L" last="Abrams">Stephen L. 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Martelli</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna</wicri:regionArea><orgName type="university">Université de Bologne</orgName><placeName><settlement type="city">Bologne</settlement><region nuts="2" type="region">Émilie-Romagne</region></placeName></affiliation></author><author><name sortKey="Ratti, Stefano" sort="Ratti, Stefano" uniqKey="Ratti S" first="Stefano" last="Ratti">Stefano Ratti</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna</wicri:regionArea><orgName type="university">Université de Bologne</orgName><placeName><settlement type="city">Bologne</settlement><region nuts="2" type="region">Émilie-Romagne</region></placeName></affiliation></author><author><name sortKey="Cocco, Lucio" sort="Cocco, Lucio" uniqKey="Cocco L" first="Lucio" last="Cocco">Lucio Cocco</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna</wicri:regionArea><orgName type="university">Université de Bologne</orgName><placeName><settlement type="city">Bologne</settlement><region nuts="2" type="region">Émilie-Romagne</region></placeName></affiliation></author><author><name sortKey="Cervello, Melchiorre" sort="Cervello, Melchiorre" uniqKey="Cervello M" first="Melchiorre" last="Cervello">Melchiorre Cervello</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo</wicri:regionArea><wicri:noRegion>Palermo</wicri:noRegion></affiliation></author><author><name sortKey="Montalto, Giuseppe" sort="Montalto, Giuseppe" uniqKey="Montalto G" first="Giuseppe" last="Montalto">Giuseppe Montalto</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo</wicri:regionArea><wicri:noRegion>Palermo</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Health Promotion, Maternal and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Health Promotion, Maternal and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo</wicri:regionArea><wicri:noRegion>Palermo</wicri:noRegion></affiliation></author><author><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation></author><author><name sortKey="Libra, Massimo" sort="Libra, Massimo" uniqKey="Libra M" first="Massimo" last="Libra">Massimo Libra</name><affiliation wicri:level="1"><nlm:affiliation>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation></author><author><name sortKey="Mccubrey, James A" sort="Mccubrey, James A" uniqKey="Mccubrey J" first="James A" last="Mccubrey">James A. Mccubrey</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32492656</idno><idno type="pmid">32492656</idno><idno type="doi">10.18632/aging.103377</idno><idno type="pmc">PMC7346063</idno><idno type="wicri:Area/Main/Corpus">000065</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000065</idno><idno type="wicri:Area/Main/Curation">000065</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000065</idno><idno type="wicri:Area/Main/Exploration">000065</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Influences of TP53 and the anti-aging DDR1 receptor in controlling Raf/MEK/ERK and PI3K/Akt expression and chemotherapeutic drug sensitivity in prostate cancer cell lines.</title><author><name sortKey="Chappell, William H" sort="Chappell, William H" uniqKey="Chappell W" first="William H" last="Chappell">William H. Chappell</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Current Address: Becton, Dickinson and Company (BD), BD Diagnostics, Franklin Lakes, NJ 07417, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Current Address: Becton, Dickinson and Company (BD), BD Diagnostics, Franklin Lakes, NJ 07417</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Candido, Saverio" sort="Candido, Saverio" uniqKey="Candido S" first="Saverio" last="Candido">Saverio Candido</name><affiliation wicri:level="1"><nlm:affiliation>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation></author><author><name sortKey="Abrams, Stephen L" sort="Abrams, Stephen L" uniqKey="Abrams S" first="Stephen L" last="Abrams">Stephen L. Abrams</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Akula, Shaw M" sort="Akula, Shaw M" uniqKey="Akula S" first="Shaw M" last="Akula">Shaw M. Akula</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Steelman, Linda S" sort="Steelman, Linda S" uniqKey="Steelman L" first="Linda S" last="Steelman">Linda S. Steelman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Martelli, Alberto M" sort="Martelli, Alberto M" uniqKey="Martelli A" first="Alberto M" last="Martelli">Alberto M. Martelli</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna</wicri:regionArea><orgName type="university">Université de Bologne</orgName><placeName><settlement type="city">Bologne</settlement><region nuts="2" type="region">Émilie-Romagne</region></placeName></affiliation></author><author><name sortKey="Ratti, Stefano" sort="Ratti, Stefano" uniqKey="Ratti S" first="Stefano" last="Ratti">Stefano Ratti</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna</wicri:regionArea><orgName type="university">Université de Bologne</orgName><placeName><settlement type="city">Bologne</settlement><region nuts="2" type="region">Émilie-Romagne</region></placeName></affiliation></author><author><name sortKey="Cocco, Lucio" sort="Cocco, Lucio" uniqKey="Cocco L" first="Lucio" last="Cocco">Lucio Cocco</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna</wicri:regionArea><orgName type="university">Université de Bologne</orgName><placeName><settlement type="city">Bologne</settlement><region nuts="2" type="region">Émilie-Romagne</region></placeName></affiliation></author><author><name sortKey="Cervello, Melchiorre" sort="Cervello, Melchiorre" uniqKey="Cervello M" first="Melchiorre" last="Cervello">Melchiorre Cervello</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo</wicri:regionArea><wicri:noRegion>Palermo</wicri:noRegion></affiliation></author><author><name sortKey="Montalto, Giuseppe" sort="Montalto, Giuseppe" uniqKey="Montalto G" first="Giuseppe" last="Montalto">Giuseppe Montalto</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo</wicri:regionArea><wicri:noRegion>Palermo</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Health Promotion, Maternal and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Health Promotion, Maternal and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo</wicri:regionArea><wicri:noRegion>Palermo</wicri:noRegion></affiliation></author><author><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation></author><author><name sortKey="Libra, Massimo" sort="Libra, Massimo" uniqKey="Libra M" first="Massimo" last="Libra">Massimo Libra</name><affiliation wicri:level="1"><nlm:affiliation>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania</wicri:regionArea><wicri:noRegion>Catania</wicri:noRegion></affiliation></author><author><name sortKey="Mccubrey, James A" sort="Mccubrey, James A" uniqKey="Mccubrey J" first="James A" last="Mccubrey">James A. Mccubrey</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author></analytic><series><title level="j">Aging</title><idno type="eISSN">1945-4589</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>TP53 plays critical roles in sensitivity to chemotherapy, and aging. Collagen is very important in aging. The molecular structure and biochemical properties of collagen changes during aging. The discoidin domain receptor (DDR1) is regulated in part by collagen. Elucidating the links between TP53 and DDR1 in chemosensitivity and aging could improve therapies against cancer and aging.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Restoration of WT-TP53 activity resulted in increased sensitivity to chemotherapeutic drugs and elevated expression of key components of the Raf/MEK/ERK, PI3K/Akt and DDR1 pathways. DDR1 could modulate the levels of Raf/MEK/ERK and PI3K/Akt pathways as well as sensitize the cells to chemotherapeutic drugs. In contrast, suppression of WT TP53 with a dominant negative (DN) TP53 gene, suppressed DDR1 protein levels and increased their chemoresistance.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Restoration of WT TP53 activity or increased expression of the anti-aging DDR1 collagen receptor can result in enhanced sensitivity to chemotherapeutic drugs. Our innovative studies indicate the important links between WT TP53 and DDR1 which can modulate Raf/MEK/ERK and PI3K/Akt signaling as well as chemosensitivity and aging.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>We investigated the roles of wild type (WT) and mutant TP53 on drug sensitivity of prostate cancer cells and the induction of Raf/MEK/ERK, PI3K/Akt and DDR1 expression and chemosensitivity.</p></div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32492656</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>01</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1945-4589</ISSN><JournalIssue CitedMedium="Internet"><Volume>12</Volume><Issue>11</Issue><PubDate><Year>2020</Year><Month>06</Month><Day>03</Day></PubDate></JournalIssue><Title>Aging</Title><ISOAbbreviation>Aging (Albany NY)</ISOAbbreviation></Journal><ArticleTitle>Influences of TP53 and the anti-aging DDR1 receptor in controlling Raf/MEK/ERK and PI3K/Akt expression and chemotherapeutic drug sensitivity in prostate cancer cell lines.</ArticleTitle><Pagination><MedlinePgn>10194-10210</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.18632/aging.103377</ELocationID><Abstract><AbstractText Label="BACKGROUND">TP53 plays critical roles in sensitivity to chemotherapy, and aging. Collagen is very important in aging. The molecular structure and biochemical properties of collagen changes during aging. The discoidin domain receptor (DDR1) is regulated in part by collagen. Elucidating the links between TP53 and DDR1 in chemosensitivity and aging could improve therapies against cancer and aging.</AbstractText><AbstractText Label="RESULTS">Restoration of WT-TP53 activity resulted in increased sensitivity to chemotherapeutic drugs and elevated expression of key components of the Raf/MEK/ERK, PI3K/Akt and DDR1 pathways. DDR1 could modulate the levels of Raf/MEK/ERK and PI3K/Akt pathways as well as sensitize the cells to chemotherapeutic drugs. In contrast, suppression of WT TP53 with a dominant negative (DN) TP53 gene, suppressed DDR1 protein levels and increased their chemoresistance.</AbstractText><AbstractText Label="CONCLUSION">Restoration of WT TP53 activity or increased expression of the anti-aging DDR1 collagen receptor can result in enhanced sensitivity to chemotherapeutic drugs. Our innovative studies indicate the important links between WT TP53 and DDR1 which can modulate Raf/MEK/ERK and PI3K/Akt signaling as well as chemosensitivity and aging.</AbstractText><AbstractText Label="METHODS">We investigated the roles of wild type (WT) and mutant TP53 on drug sensitivity of prostate cancer cells and the induction of Raf/MEK/ERK, PI3K/Akt and DDR1 expression and chemosensitivity.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chappell</LastName><ForeName>William H</ForeName><Initials>WH</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Current Address: Becton, Dickinson and Company (BD), BD Diagnostics, Franklin Lakes, NJ 07417, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Candido</LastName><ForeName>Saverio</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abrams</LastName><ForeName>Stephen L</ForeName><Initials>SL</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Akula</LastName><ForeName>Shaw M</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Steelman</LastName><ForeName>Linda S</ForeName><Initials>LS</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Martelli</LastName><ForeName>Alberto M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ratti</LastName><ForeName>Stefano</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cocco</LastName><ForeName>Lucio</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cervello</LastName><ForeName>Melchiorre</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Montalto</LastName><ForeName>Giuseppe</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Institute for Biomedical Research and Innovation, National Research Council (CNR), Palermo, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Health Promotion, Maternal and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nicoletti</LastName><ForeName>Ferdinando</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Libra</LastName><ForeName>Massimo</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, Catania, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McCubrey</LastName><ForeName>James A</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>06</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Aging (Albany NY)</MedlineTA><NlmUniqueID>101508617</NlmUniqueID><ISSNLinking>1945-4589</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">DDR</Keyword><Keyword MajorTopicYN="Y">RAF/MEK/ERK</Keyword><Keyword MajorTopicYN="Y">TP53</Keyword><Keyword MajorTopicYN="Y">collagen</Keyword><Keyword MajorTopicYN="Y">rapamycin</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>12</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>05</Month><Day>20</Day></PubMedPubDate><PubMedPubDate 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Martelli</name><name sortKey="Montalto, Giuseppe" sort="Montalto, Giuseppe" uniqKey="Montalto G" first="Giuseppe" last="Montalto">Giuseppe Montalto</name><name sortKey="Montalto, Giuseppe" sort="Montalto, Giuseppe" uniqKey="Montalto G" first="Giuseppe" last="Montalto">Giuseppe Montalto</name><name sortKey="Nicoletti, Ferdinando" sort="Nicoletti, Ferdinando" uniqKey="Nicoletti F" first="Ferdinando" last="Nicoletti">Ferdinando Nicoletti</name><name sortKey="Ratti, Stefano" sort="Ratti, Stefano" uniqKey="Ratti S" first="Stefano" last="Ratti">Stefano Ratti</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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