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Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide
Acid ceramidase (AC) over-expression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC over-expression is the ability to convert ceramide, which is often produced as a pro-apoptotic response to stres...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203650/ https://www.ncbi.nlm.nih.gov/pubmed/21116286 http://dx.doi.org/10.1038/pcan.2010.47 |
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author | Turner, Lorianne S. Cheng, Joseph C. Beckham, Thomas H. Norris, James S. Liu, Xiang |
author_facet | Turner, Lorianne S. Cheng, Joseph C. Beckham, Thomas H. Norris, James S. Liu, Xiang |
author_sort | Turner, Lorianne S. |
collection | PubMed |
description | Acid ceramidase (AC) over-expression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC over-expression is the ability to convert ceramide, which is often produced as a pro-apoptotic response to stress, to sphingosine, which can then be converted to the pro-survival molecule sphingosine-1-phosphate. In addition to their ability to metabolize ceramide produced in response to stress, we show here that prostate cancer cell lines over-expressing acid ceramidase also have increased lysosomal density and increased levels of autophagy. Furthermore, pre-treatment with 3-methyladenine restores sensitivity of these cells to treatment with C(6)-ceramide. We also observed increased expression of the lysosomal stabilizing protein KIF5B and increased sensitivity to the lysosomotropic agent LCL385. Thus, we conclude that acid ceramidase over-expression increases autophagy in prostate cancer cells, and that increased autophagy enhances resistance to ceramide. |
format | Online Article Text |
id | pubmed-4203650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
spelling | pubmed-42036502014-10-20 Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide Turner, Lorianne S. Cheng, Joseph C. Beckham, Thomas H. Norris, James S. Liu, Xiang Prostate Cancer Prostatic Dis Article Acid ceramidase (AC) over-expression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC over-expression is the ability to convert ceramide, which is often produced as a pro-apoptotic response to stress, to sphingosine, which can then be converted to the pro-survival molecule sphingosine-1-phosphate. In addition to their ability to metabolize ceramide produced in response to stress, we show here that prostate cancer cell lines over-expressing acid ceramidase also have increased lysosomal density and increased levels of autophagy. Furthermore, pre-treatment with 3-methyladenine restores sensitivity of these cells to treatment with C(6)-ceramide. We also observed increased expression of the lysosomal stabilizing protein KIF5B and increased sensitivity to the lysosomotropic agent LCL385. Thus, we conclude that acid ceramidase over-expression increases autophagy in prostate cancer cells, and that increased autophagy enhances resistance to ceramide. 2010-11-30 2011-03 /pmc/articles/PMC4203650/ /pubmed/21116286 http://dx.doi.org/10.1038/pcan.2010.47 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Turner, Lorianne S. Cheng, Joseph C. Beckham, Thomas H. Norris, James S. Liu, Xiang Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide |
title | Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide |
title_full | Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide |
title_fullStr | Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide |
title_full_unstemmed | Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide |
title_short | Autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to C(6)-ceramide |
title_sort | autophagy is increased in prostate cancer cells over-expressing acid ceramidase and enhances resistance to c(6)-ceramide |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203650/ https://www.ncbi.nlm.nih.gov/pubmed/21116286 http://dx.doi.org/10.1038/pcan.2010.47 |
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