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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...

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Autores principales: Han, Kyung Ho, Kwak, Minseok, Lee, Tae Hyeong, Park, Min-soo, Jeong, In-ho, Kim, Min Ji, Jin, Jun-O, Lee, Peter Chang-Whan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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