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A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas
Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resis...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999293/ https://www.ncbi.nlm.nih.gov/pubmed/29897944 http://dx.doi.org/10.1371/journal.pone.0197610 |
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author | Adams, Olivia Janser, Félice A. Dislich, Bastian Berezowska, Sabina Humbert, Magali Seiler, Christian A. Kroell, Dino Slotta-Huspenina, Julia Feith, Marcus Ott, Katja Tschan, Mario P. Langer, Rupert |
author_facet | Adams, Olivia Janser, Félice A. Dislich, Bastian Berezowska, Sabina Humbert, Magali Seiler, Christian A. Kroell, Dino Slotta-Huspenina, Julia Feith, Marcus Ott, Katja Tschan, Mario P. Langer, Rupert |
author_sort | Adams, Olivia |
collection | PubMed |
description | Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resistance. We aimed to assess the impact of autophagy on chemotherapy response in EAC, with a special focus on paclitaxel. Responsiveness of EAC cell lines, OE19, FLO-1, OE33 and SK-GT-4, to paclitaxel was assessed using Alamar Blue assays. Autophagic flux upon paclitaxel treatment in vitro was assessed by immunoblotting of LC3B-II and quantitative assessment of WIP1 mRNA. Immunohistochemistry for the autophagy markers LC3B and p62 was applied on tumor tissue from 149 EAC patients treated with neoadjuvant chemotherapy, including pre- and post-therapeutic samples (62 matched pairs). Tumor response was assessed by histology. For comparison, previously published data on 114 primary resected EAC cases were used. EAC cell lines displayed differing responsiveness to paclitaxel treatment; however this was not associated with differential autophagy regulation. High p62 cytoplasmic expression on its own (p ≤ 0.001), or in combination with low LC3B (p = 0.034), was associated with nonresponse to chemotherapy, regardless of whether or not the regiments contained paclitaxel, but there was no independent prognostic value of LC3B or p62 expression patterns for EAC after neoadjuvant treatment. p62 and related pathways, most likely other than autophagy, play a role in chemotherapeutic response in EAC in a clinical setting. Therefore p62 could be a novel therapeutic target to overcome chemoresistance in EAC. |
format | Online Article Text |
id | pubmed-5999293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-59992932018-06-21 A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas Adams, Olivia Janser, Félice A. Dislich, Bastian Berezowska, Sabina Humbert, Magali Seiler, Christian A. Kroell, Dino Slotta-Huspenina, Julia Feith, Marcus Ott, Katja Tschan, Mario P. Langer, Rupert PLoS One Research Article Paclitaxel is a powerful chemotherapeutic drug, used for the treatment of many cancer types, including esophageal adenocarcinomas (EAC). Autophagy is a lysosome-dependent degradation process maintaining cellular homeostasis. Defective autophagy has been implicated in cancer biology and therapy resistance. We aimed to assess the impact of autophagy on chemotherapy response in EAC, with a special focus on paclitaxel. Responsiveness of EAC cell lines, OE19, FLO-1, OE33 and SK-GT-4, to paclitaxel was assessed using Alamar Blue assays. Autophagic flux upon paclitaxel treatment in vitro was assessed by immunoblotting of LC3B-II and quantitative assessment of WIP1 mRNA. Immunohistochemistry for the autophagy markers LC3B and p62 was applied on tumor tissue from 149 EAC patients treated with neoadjuvant chemotherapy, including pre- and post-therapeutic samples (62 matched pairs). Tumor response was assessed by histology. For comparison, previously published data on 114 primary resected EAC cases were used. EAC cell lines displayed differing responsiveness to paclitaxel treatment; however this was not associated with differential autophagy regulation. High p62 cytoplasmic expression on its own (p ≤ 0.001), or in combination with low LC3B (p = 0.034), was associated with nonresponse to chemotherapy, regardless of whether or not the regiments contained paclitaxel, but there was no independent prognostic value of LC3B or p62 expression patterns for EAC after neoadjuvant treatment. p62 and related pathways, most likely other than autophagy, play a role in chemotherapeutic response in EAC in a clinical setting. Therefore p62 could be a novel therapeutic target to overcome chemoresistance in EAC. Public Library of Science 2018-06-13 /pmc/articles/PMC5999293/ /pubmed/29897944 http://dx.doi.org/10.1371/journal.pone.0197610 Text en © 2018 Adams et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Adams, Olivia Janser, Félice A. Dislich, Bastian Berezowska, Sabina Humbert, Magali Seiler, Christian A. Kroell, Dino Slotta-Huspenina, Julia Feith, Marcus Ott, Katja Tschan, Mario P. Langer, Rupert A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas |
title | A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas |
title_full | A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas |
title_fullStr | A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas |
title_full_unstemmed | A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas |
title_short | A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas |
title_sort | specific expression profile of lc3b and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999293/ https://www.ncbi.nlm.nih.gov/pubmed/29897944 http://dx.doi.org/10.1371/journal.pone.0197610 |
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