SOX2 as a novel contributor of oxidative metabolism in melanoma cells
Abstract Background Deregulated metabolism is a hallmark of cancer and recent evidence underlines that targeting tumor energetics may improve therapy response and patient outcome. Despite the general attitude of cancer cells to exploit the glycolytic pathway even in the presence of oxygen (aerobic g...
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | http://link.springer.com/article/10.1186/s12964-018-0297-z |
| _version_ | 1818228906908450816 |
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| author | Elena Andreucci Silvia Pietrobono Silvia Peppicelli Jessica Ruzzolini Francesca Bianchini Alessio Biagioni Barbara Stecca Lido Calorini |
| author_facet | Elena Andreucci Silvia Pietrobono Silvia Peppicelli Jessica Ruzzolini Francesca Bianchini Alessio Biagioni Barbara Stecca Lido Calorini |
| author_sort | Elena Andreucci |
| collection | DOAJ |
| description | Abstract Background Deregulated metabolism is a hallmark of cancer and recent evidence underlines that targeting tumor energetics may improve therapy response and patient outcome. Despite the general attitude of cancer cells to exploit the glycolytic pathway even in the presence of oxygen (aerobic glycolysis or “Warburg effect”), tumor metabolism is extremely plastic, and such ability to switch from glycolysis to oxidative phosphorylation (OxPhos) allows cancer cells to survive under hostile microenvironments. Recently, OxPhos has been related with malignant progression, chemo-resistance and metastasis. OxPhos is induced under extracellular acidosis, a well-known characteristic of most solid tumors, included melanoma. Methods To evaluate whether SOX2 modulation is correlated with metabolic changes under standard or acidic conditions, SOX2 was silenced and overexpressed in several melanoma cell lines. To demonstrate that SOX2 directly represses HIF1A expression we used chromatin immunoprecipitation (ChIP) and luciferase assay. Results In A375-M6 melanoma cells, extracellular acidosis increases SOX2 expression, that sustains the oxidative cancer metabolism exploited under acidic conditions. By studying non-acidic SSM2c and 501-Mel melanoma cells (high- and very low-SOX2 expressing cells, respectively), we confirmed the metabolic role of SOX2, attributing SOX2-driven OxPhos reprogramming to HIF1α pathway disruption. Conclusions SOX2 contributes to the acquisition of an aggressive oxidative tumor phenotype, endowed with enhanced drug resistance and metastatic ability. |
| first_indexed | 2024-12-12T10:10:09Z |
| format | Article |
| id | doaj.art-4a51086552cd4cd5acc24c0ee2ace7c6 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-12T10:10:09Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-4a51086552cd4cd5acc24c0ee2ace7c62022-12-22T00:27:49ZengBMCCell Communication and Signaling1478-811X2018-11-0116111310.1186/s12964-018-0297-zSOX2 as a novel contributor of oxidative metabolism in melanoma cellsElena Andreucci0Silvia Pietrobono1Silvia Peppicelli2Jessica Ruzzolini3Francesca Bianchini4Alessio Biagioni5Barbara Stecca6Lido Calorini7Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, Section of Experimental Pathology and Oncology, University of FlorenceCore Research Laboratory, Institute for Cancer Research and Prevention (ISPRO)Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, Section of Experimental Pathology and Oncology, University of FlorenceDepartment of Clinical and Experimental Biomedical Sciences “Mario Serio”, Section of Experimental Pathology and Oncology, University of FlorenceDepartment of Clinical and Experimental Biomedical Sciences “Mario Serio”, Section of Experimental Pathology and Oncology, University of FlorenceDepartment of Clinical and Experimental Biomedical Sciences “Mario Serio”, Section of Experimental Pathology and Oncology, University of FlorenceCore Research Laboratory, Institute for Cancer Research and Prevention (ISPRO)Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, Section of Experimental Pathology and Oncology, University of FlorenceAbstract Background Deregulated metabolism is a hallmark of cancer and recent evidence underlines that targeting tumor energetics may improve therapy response and patient outcome. Despite the general attitude of cancer cells to exploit the glycolytic pathway even in the presence of oxygen (aerobic glycolysis or “Warburg effect”), tumor metabolism is extremely plastic, and such ability to switch from glycolysis to oxidative phosphorylation (OxPhos) allows cancer cells to survive under hostile microenvironments. Recently, OxPhos has been related with malignant progression, chemo-resistance and metastasis. OxPhos is induced under extracellular acidosis, a well-known characteristic of most solid tumors, included melanoma. Methods To evaluate whether SOX2 modulation is correlated with metabolic changes under standard or acidic conditions, SOX2 was silenced and overexpressed in several melanoma cell lines. To demonstrate that SOX2 directly represses HIF1A expression we used chromatin immunoprecipitation (ChIP) and luciferase assay. Results In A375-M6 melanoma cells, extracellular acidosis increases SOX2 expression, that sustains the oxidative cancer metabolism exploited under acidic conditions. By studying non-acidic SSM2c and 501-Mel melanoma cells (high- and very low-SOX2 expressing cells, respectively), we confirmed the metabolic role of SOX2, attributing SOX2-driven OxPhos reprogramming to HIF1α pathway disruption. Conclusions SOX2 contributes to the acquisition of an aggressive oxidative tumor phenotype, endowed with enhanced drug resistance and metastatic ability.http://link.springer.com/article/10.1186/s12964-018-0297-zMelanomaTumor extracellular acidosisSOX2HIF1αOxidative metabolism |
| spellingShingle | Elena Andreucci Silvia Pietrobono Silvia Peppicelli Jessica Ruzzolini Francesca Bianchini Alessio Biagioni Barbara Stecca Lido Calorini SOX2 as a novel contributor of oxidative metabolism in melanoma cells Cell Communication and Signaling Melanoma Tumor extracellular acidosis SOX2 HIF1α Oxidative metabolism |
| title | SOX2 as a novel contributor of oxidative metabolism in melanoma cells |
| title_full | SOX2 as a novel contributor of oxidative metabolism in melanoma cells |
| title_fullStr | SOX2 as a novel contributor of oxidative metabolism in melanoma cells |
| title_full_unstemmed | SOX2 as a novel contributor of oxidative metabolism in melanoma cells |
| title_short | SOX2 as a novel contributor of oxidative metabolism in melanoma cells |
| title_sort | sox2 as a novel contributor of oxidative metabolism in melanoma cells |
| topic | Melanoma Tumor extracellular acidosis SOX2 HIF1α Oxidative metabolism |
| url | http://link.springer.com/article/10.1186/s12964-018-0297-z |
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