Cargando…
Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2
Pyruvate kinase M2 (PKM2), a glycolytic enzyme, acts as a metabolic function leading to an energy production critical for cancer progression, known as Warburg effect. In this study we showed a pivotal role of PKM2 acting as a non-metabolic function to promote cancer cell progression in human oral sq...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173467/ https://www.ncbi.nlm.nih.gov/pubmed/30333907 http://dx.doi.org/10.18632/oncotarget.25850 |
_version_ | 1783361137370202112 |
---|---|
author | Tanaka, Fumie Yoshimoto, Shohei Okamura, Kazuhiko Ikebe, Tetsuro Hashimoto, Shuichi |
author_facet | Tanaka, Fumie Yoshimoto, Shohei Okamura, Kazuhiko Ikebe, Tetsuro Hashimoto, Shuichi |
author_sort | Tanaka, Fumie |
collection | PubMed |
description | Pyruvate kinase M2 (PKM2), a glycolytic enzyme, acts as a metabolic function leading to an energy production critical for cancer progression, known as Warburg effect. In this study we showed a pivotal role of PKM2 acting as a non-metabolic function to promote cancer cell progression in human oral squamous cell carcinoma (OSCC) through the induction of epithelial-mesenchymal transition (EMT), which is crucial for the potential in cancer cell invasion, and post-translational TGIF2 degradation. PKM2 immunoreaction was strong in the cytoplasm of invasive cancer cells, and distinct in the nucleus of spindle-shaped cancer cells with EMT characteristics. TGIF2 nuclear immunoreaction was seen in dysplastic epithelial cells but was repressed in cancer cells. In vitro analyses, cytoplasmic expression of PKM2 was translocated into the nucleus in human OSCC derived HSC-4 and SAS cells when EMT was stimulated. In addition, nuclear expression of TGIF2 was distinctively repressed in EMT induced HSC-4 and SAS cells. We recognized a mismatch in TGIF2 protein and mRNA expression in EMT induced HSC-4 and SAS cells and found that TGIF2 protein was post-translationally degraded through a ubiquitin proteasome system by an MG132 proteasome inhibition assay. Finally, promotion of HSC-4 and SAS cell progression by PKM2 was recognized in PKM2 knockdown assays. Thus, we clarified a new mechanism of non-metabolic function of PKM2 to promote the progression of OSCC through PKM2 nuclear translocation, subsequently induced EMT, and post-translationally repressed TGIF2 expression by a ubiquitin proteasome system. |
format | Online Article Text |
id | pubmed-6173467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-61734672018-10-17 Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2 Tanaka, Fumie Yoshimoto, Shohei Okamura, Kazuhiko Ikebe, Tetsuro Hashimoto, Shuichi Oncotarget Research Paper Pyruvate kinase M2 (PKM2), a glycolytic enzyme, acts as a metabolic function leading to an energy production critical for cancer progression, known as Warburg effect. In this study we showed a pivotal role of PKM2 acting as a non-metabolic function to promote cancer cell progression in human oral squamous cell carcinoma (OSCC) through the induction of epithelial-mesenchymal transition (EMT), which is crucial for the potential in cancer cell invasion, and post-translational TGIF2 degradation. PKM2 immunoreaction was strong in the cytoplasm of invasive cancer cells, and distinct in the nucleus of spindle-shaped cancer cells with EMT characteristics. TGIF2 nuclear immunoreaction was seen in dysplastic epithelial cells but was repressed in cancer cells. In vitro analyses, cytoplasmic expression of PKM2 was translocated into the nucleus in human OSCC derived HSC-4 and SAS cells when EMT was stimulated. In addition, nuclear expression of TGIF2 was distinctively repressed in EMT induced HSC-4 and SAS cells. We recognized a mismatch in TGIF2 protein and mRNA expression in EMT induced HSC-4 and SAS cells and found that TGIF2 protein was post-translationally degraded through a ubiquitin proteasome system by an MG132 proteasome inhibition assay. Finally, promotion of HSC-4 and SAS cell progression by PKM2 was recognized in PKM2 knockdown assays. Thus, we clarified a new mechanism of non-metabolic function of PKM2 to promote the progression of OSCC through PKM2 nuclear translocation, subsequently induced EMT, and post-translationally repressed TGIF2 expression by a ubiquitin proteasome system. Impact Journals LLC 2018-09-18 /pmc/articles/PMC6173467/ /pubmed/30333907 http://dx.doi.org/10.18632/oncotarget.25850 Text en Copyright: © 2018 Tanaka et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Tanaka, Fumie Yoshimoto, Shohei Okamura, Kazuhiko Ikebe, Tetsuro Hashimoto, Shuichi Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2 |
title | Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2 |
title_full | Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2 |
title_fullStr | Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2 |
title_full_unstemmed | Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2 |
title_short | Nuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2 |
title_sort | nuclear pkm2 promotes the progression of oral squamous cell carcinoma by inducing emt and post-translationally repressing tgif2 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173467/ https://www.ncbi.nlm.nih.gov/pubmed/30333907 http://dx.doi.org/10.18632/oncotarget.25850 |
work_keys_str_mv | AT tanakafumie nuclearpkm2promotestheprogressionoforalsquamouscellcarcinomabyinducingemtandposttranslationallyrepressingtgif2 AT yoshimotoshohei nuclearpkm2promotestheprogressionoforalsquamouscellcarcinomabyinducingemtandposttranslationallyrepressingtgif2 AT okamurakazuhiko nuclearpkm2promotestheprogressionoforalsquamouscellcarcinomabyinducingemtandposttranslationallyrepressingtgif2 AT ikebetetsuro nuclearpkm2promotestheprogressionoforalsquamouscellcarcinomabyinducingemtandposttranslationallyrepressingtgif2 AT hashimotoshuichi nuclearpkm2promotestheprogressionoforalsquamouscellcarcinomabyinducingemtandposttranslationallyrepressingtgif2 |