Cytoplasmic translocation of p21 mediates NUPR1‐induced chemoresistance
Copyright policy )Cytoplasmic translocation of p21 mediates NUPR1‐induced chemoresistance
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.
- University of South Alabama United States
- University of Alabama at Birmingham United States
- University of Oslo Norway
- USA Mitchell Cancer Institute United States
- Oslo University Hospital Norway
Basic Helix-Loop-Helix Proteins, Cyclin-Dependent Kinase Inhibitor p21, Cytoplasm, P21, bcl-X Protein, Biological Transport, Active, Breast Neoplasms, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Humans, Phosphorylation, Akt, Nuclear Proteins, Neoplasm Proteins, Oncogene Protein v-akt, IKK-β, Doxorubicin, Drug Resistance, Neoplasm, Female, Tumor Suppressor Protein p53, NUPR1, Chemoresistance, Signal Transduction
Basic Helix-Loop-Helix Proteins, Cyclin-Dependent Kinase Inhibitor p21, Cytoplasm, P21, bcl-X Protein, Biological Transport, Active, Breast Neoplasms, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Humans, Phosphorylation, Akt, Nuclear Proteins, Neoplasm Proteins, Oncogene Protein v-akt, IKK-β, Doxorubicin, Drug Resistance, Neoplasm, Female, Tumor Suppressor Protein p53, NUPR1, Chemoresistance, Signal Transduction
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