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Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma
Although cytoplasmic AMP-activated protein kinase (AMPK) has been known as a tumor-suppressor protein, nuclear AMPK is suggested to support clear cell renal cell carcinoma (ccRCC). In addition, pAMPK interacts with TGF-β/SMAD, which is one of the frequently altered pathways in ccRCC. In this study,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826619/ https://www.ncbi.nlm.nih.gov/pubmed/31640193 http://dx.doi.org/10.3390/cancers11101602 |
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author | Jung, Minsun Lee, Jeong Hoon Lee, Cheol Park, Jeong Hwan Park, Yu Rang Moon, Kyung Chul |
author_facet | Jung, Minsun Lee, Jeong Hoon Lee, Cheol Park, Jeong Hwan Park, Yu Rang Moon, Kyung Chul |
author_sort | Jung, Minsun |
collection | PubMed |
description | Although cytoplasmic AMP-activated protein kinase (AMPK) has been known as a tumor-suppressor protein, nuclear AMPK is suggested to support clear cell renal cell carcinoma (ccRCC). In addition, pAMPK interacts with TGF-β/SMAD, which is one of the frequently altered pathways in ccRCC. In this study, we investigated the prognostic significance of pAMPK with respect to subcellular location and investigated its interaction with TGF-β/SMAD in ccRCC. Immunohistochemical staining for pAMPK, pSMAD2 and SMAD4 was conducted on tissue microarray of 987 ccRCC specimens. Moreover, the levels of pSMAD2 were measured in Caki-1 cells treated with 5-aminoimidazole-4-carboxamide ribonucleotide. The relationship between AMPK/pAMPK and TGFB1 expression was determined using the TCGA database. As a result, pAMPK positivity, either in the cytoplasm or nuclei, was independently associated with improved ccRCC prognosis, after adjusting for TNM stage and WHO grade. Furthermore, pAMPK-positive ccRCC displayed increased pSMAD2 and SMAD4 expression, while activation of pAMPK increased pSMAD2 in Caki-1 cells. However, AMPK/pAMPK expression was inversely correlated with TGFB1 expression in the TCGA database. Therefore, pAMPK immunostaining, both in the cytoplasm and nuclei, is a useful prognostic biomarker for ccRCC. pAMPK targets TGF-β-independent phosphorylation of SMAD2 and activates pSMAD2/SMAD4, representing a novel anti-tumoral mechanism of pAMPK in ccRCC. |
format | Online Article Text |
id | pubmed-6826619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68266192019-11-18 Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma Jung, Minsun Lee, Jeong Hoon Lee, Cheol Park, Jeong Hwan Park, Yu Rang Moon, Kyung Chul Cancers (Basel) Article Although cytoplasmic AMP-activated protein kinase (AMPK) has been known as a tumor-suppressor protein, nuclear AMPK is suggested to support clear cell renal cell carcinoma (ccRCC). In addition, pAMPK interacts with TGF-β/SMAD, which is one of the frequently altered pathways in ccRCC. In this study, we investigated the prognostic significance of pAMPK with respect to subcellular location and investigated its interaction with TGF-β/SMAD in ccRCC. Immunohistochemical staining for pAMPK, pSMAD2 and SMAD4 was conducted on tissue microarray of 987 ccRCC specimens. Moreover, the levels of pSMAD2 were measured in Caki-1 cells treated with 5-aminoimidazole-4-carboxamide ribonucleotide. The relationship between AMPK/pAMPK and TGFB1 expression was determined using the TCGA database. As a result, pAMPK positivity, either in the cytoplasm or nuclei, was independently associated with improved ccRCC prognosis, after adjusting for TNM stage and WHO grade. Furthermore, pAMPK-positive ccRCC displayed increased pSMAD2 and SMAD4 expression, while activation of pAMPK increased pSMAD2 in Caki-1 cells. However, AMPK/pAMPK expression was inversely correlated with TGFB1 expression in the TCGA database. Therefore, pAMPK immunostaining, both in the cytoplasm and nuclei, is a useful prognostic biomarker for ccRCC. pAMPK targets TGF-β-independent phosphorylation of SMAD2 and activates pSMAD2/SMAD4, representing a novel anti-tumoral mechanism of pAMPK in ccRCC. MDPI 2019-10-21 /pmc/articles/PMC6826619/ /pubmed/31640193 http://dx.doi.org/10.3390/cancers11101602 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jung, Minsun Lee, Jeong Hoon Lee, Cheol Park, Jeong Hwan Park, Yu Rang Moon, Kyung Chul Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma |
title | Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma |
title_full | Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma |
title_fullStr | Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma |
title_full_unstemmed | Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma |
title_short | Prognostic Implication of pAMPK Immunohistochemical Staining by Subcellular Location and Its Association with SMAD Protein Expression in Clear Cell Renal Cell Carcinoma |
title_sort | prognostic implication of pampk immunohistochemical staining by subcellular location and its association with smad protein expression in clear cell renal cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826619/ https://www.ncbi.nlm.nih.gov/pubmed/31640193 http://dx.doi.org/10.3390/cancers11101602 |
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