biostudies-literatureUnknown9(73)Tanaka FPyruvate 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. <i>In vitro</i> 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.Oncotarget33745-33761https://www.ebi.ac.uk/biostudies/studies/S-EPMC6173467biostudies-literatureNuclear PKM2 promotes the progression of oral squamous cell carcinoma by inducing EMT and post-translationally repressing TGIF2.PMC6173467Ikebe TTanaka FHashimoto SOkamura KYoshimoto SfalseNuclear 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 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. <i>In vitro</i> 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.2018-01-01T00:00:00Z2018 Sep2024-10-19T05:25:13.958Z2019-03-27T00:03:01ZS-EPMC61734673033390710.18632/oncotarget.25850