Cargando…

Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells

In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresis...

Descripción completa

Detalles Bibliográficos
Autores principales: Matsumoto, Ryuji, Tsuda, Masumi, Yoshida, Kazuhiko, Tanino, Mishie, Kimura, Taichi, Nishihara, Hiroshi, Abe, Takashige, Shinohara, Nobuo, Nonomura, Katsuya, Tanaka, Shinya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048132/
https://www.ncbi.nlm.nih.gov/pubmed/27698389
http://dx.doi.org/10.1038/srep34625
_version_ 1782457544384446464
author Matsumoto, Ryuji
Tsuda, Masumi
Yoshida, Kazuhiko
Tanino, Mishie
Kimura, Taichi
Nishihara, Hiroshi
Abe, Takashige
Shinohara, Nobuo
Nonomura, Katsuya
Tanaka, Shinya
author_facet Matsumoto, Ryuji
Tsuda, Masumi
Yoshida, Kazuhiko
Tanino, Mishie
Kimura, Taichi
Nishihara, Hiroshi
Abe, Takashige
Shinohara, Nobuo
Nonomura, Katsuya
Tanaka, Shinya
author_sort Matsumoto, Ryuji
collection PubMed
description In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment.
format Online
Article
Text
id pubmed-5048132
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-50481322016-10-11 Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells Matsumoto, Ryuji Tsuda, Masumi Yoshida, Kazuhiko Tanino, Mishie Kimura, Taichi Nishihara, Hiroshi Abe, Takashige Shinohara, Nobuo Nonomura, Katsuya Tanaka, Shinya Sci Rep Article In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment. Nature Publishing Group 2016-10-04 /pmc/articles/PMC5048132/ /pubmed/27698389 http://dx.doi.org/10.1038/srep34625 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Matsumoto, Ryuji
Tsuda, Masumi
Yoshida, Kazuhiko
Tanino, Mishie
Kimura, Taichi
Nishihara, Hiroshi
Abe, Takashige
Shinohara, Nobuo
Nonomura, Katsuya
Tanaka, Shinya
Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells
title Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells
title_full Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells
title_fullStr Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells
title_full_unstemmed Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells
title_short Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells
title_sort aldo-keto reductase 1c1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048132/
https://www.ncbi.nlm.nih.gov/pubmed/27698389
http://dx.doi.org/10.1038/srep34625
work_keys_str_mv AT matsumotoryuji aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT tsudamasumi aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT yoshidakazuhiko aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT taninomishie aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT kimurataichi aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT nishiharahiroshi aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT abetakashige aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT shinoharanobuo aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT nonomurakatsuya aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells
AT tanakashinya aldoketoreductase1c1inducedbyinterleukin1bmediatestheinvasivepotentialanddrugresistanceofmetastaticbladdercancercells