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USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro
The ubiquitin–proteasome system is an essential regulator of several cellular pathways involving oncogenes. Deubiquitination negatively regulates target proteins or substrates linked to both hereditary and sporadic forms of cancer. The deubiquitinating enzyme ubiquitin-specific protease 14 (USP14) i...
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/PMC6862215/ https://www.ncbi.nlm.nih.gov/pubmed/31653087 http://dx.doi.org/10.3390/ijms20215300 |
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author | Han, Kyung Ho Kwak, Minseok Lee, Tae Hyeong Park, Min-soo Jeong, In-ho Kim, Min Ji Jin, Jun-O Lee, Peter Chang-Whan |
author_facet | Han, Kyung Ho Kwak, Minseok Lee, Tae Hyeong Park, Min-soo Jeong, In-ho Kim, Min Ji Jin, Jun-O Lee, Peter Chang-Whan |
author_sort | Han, Kyung Ho |
collection | PubMed |
description | The ubiquitin–proteasome system is an essential regulator of several cellular pathways involving oncogenes. Deubiquitination negatively regulates target proteins or substrates linked to both hereditary and sporadic forms of cancer. The deubiquitinating enzyme ubiquitin-specific protease 14 (USP14) is associated with proteasomes where it trims the ubiquitin chain on the substrate. Here, we found that USP14 is highly expressed in patients with lung cancer. We also demonstrated that USP14 inhibitors (IU1-47 and siRNA-USP14) significantly decreased cell proliferation, migration, and invasion in lung cancer. Remarkably, we found that USP14 negatively regulates lung tumorigenesis not only through apoptosis but also through the autophagy pathway. Our findings suggest that USP14 plays a crucial role in lung tumorigenesis and that USP14 inhibitors are potent drugs in lung cancer treatment. |
format | Online Article Text |
id | pubmed-6862215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68622152019-12-05 USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro Han, Kyung Ho Kwak, Minseok Lee, Tae Hyeong Park, Min-soo Jeong, In-ho Kim, Min Ji Jin, Jun-O Lee, Peter Chang-Whan Int J Mol Sci Article The ubiquitin–proteasome system is an essential regulator of several cellular pathways involving oncogenes. Deubiquitination negatively regulates target proteins or substrates linked to both hereditary and sporadic forms of cancer. The deubiquitinating enzyme ubiquitin-specific protease 14 (USP14) is associated with proteasomes where it trims the ubiquitin chain on the substrate. Here, we found that USP14 is highly expressed in patients with lung cancer. We also demonstrated that USP14 inhibitors (IU1-47 and siRNA-USP14) significantly decreased cell proliferation, migration, and invasion in lung cancer. Remarkably, we found that USP14 negatively regulates lung tumorigenesis not only through apoptosis but also through the autophagy pathway. Our findings suggest that USP14 plays a crucial role in lung tumorigenesis and that USP14 inhibitors are potent drugs in lung cancer treatment. MDPI 2019-10-24 /pmc/articles/PMC6862215/ /pubmed/31653087 http://dx.doi.org/10.3390/ijms20215300 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 Han, Kyung Ho Kwak, Minseok Lee, Tae Hyeong Park, Min-soo Jeong, In-ho Kim, Min Ji Jin, Jun-O Lee, Peter Chang-Whan USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro |
title | USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro |
title_full | USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro |
title_fullStr | USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro |
title_full_unstemmed | USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro |
title_short | USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro |
title_sort | usp14 inhibition regulates tumorigenesis by inducing autophagy in lung cancer in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862215/ https://www.ncbi.nlm.nih.gov/pubmed/31653087 http://dx.doi.org/10.3390/ijms20215300 |
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