title: Cytoplasmic translocation of p21 mediates NUPR1-induced chemoresistance: NUPR1 and p21 in chemoresistance.
abstract: The expression of Nuclear Protein 1 (NUPR1) is associated with chemoresistance in multiple malignancies. We previously reported that NUPR1 functions as a transcriptional cofactor for the p300-p53 complex and transcriptionally regulates p21 expression. In the present study we investigated the activity of NUPR1 in p53-deficient, triple-negative, inflammatory SUM159 breast cancer cells. Our studies reveal that NUPR1 confers growth benefit and chemoresistance by causing Akt-mediated phosphorylation and subsequent cytoplasmic re-localization of p21 and activation of the anti-apoptotic Bcl-xL protein. Our findings elucidate a NUPR1-PI-3-K/Akt-phospho-p21 axis that functions in p53-negative, inflammatory breast cancer cells to enhance chemoresistance in breast cancer.
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Vincent
authors.forename: Suping
authors.initials: S
authors.lastname: Ren
authors.forename: Lillianne G
authors.initials: LG
authors.lastname: Harris
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Devine
authors.forename: Rajeev S
authors.initials: RS
authors.lastname: Samant
authors.forename: Oystein
authors.initials: O
authors.lastname: Fodstad
authors.forename: Lalita A
authors.initials: LA
authors.lastname: Shevde
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001693:Biological Transport, Active; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004317:Doxorubicin; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; C494811:BCL2L1 protein, human; C493956:CDKN1A protein, human; C491643:NUPR1 protein, human; C495901:TP53 protein, human