PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells
Background: Enhanced glycolysis occurs in most human cancer cells and is related to chemoresistance. However, detailed mechanisms remain vague. Methods: Using proteinomics analysis, we found that the glycolytic enzyme Phosphoglycerate mutase 1 (PGAM1) was highly expressed in the paclitaxel-resistant...
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| Format: | Article |
| Language: | English |
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IMR Press
2022-09-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/27/9/10.31083/j.fbl2709262 |
| _version_ | 1828105804316672000 |
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| author | Yan Feng Xu Zhang Songfa Zhang Shanshan Xu Xiaojing Chen Caiyun Zhou Yongmei Xi Xing Xie Weiguo Lu |
| author_facet | Yan Feng Xu Zhang Songfa Zhang Shanshan Xu Xiaojing Chen Caiyun Zhou Yongmei Xi Xing Xie Weiguo Lu |
| author_sort | Yan Feng |
| collection | DOAJ |
| description | Background: Enhanced glycolysis occurs in most human cancer cells and is related to chemoresistance. However, detailed mechanisms remain vague. Methods: Using proteinomics analysis, we found that the glycolytic enzyme Phosphoglycerate mutase 1 (PGAM1) was highly expressed in the paclitaxel-resistant ovarian cancer cell line SKOV3-TR30, as compared to its parental cell line SKOV3. Cell Counting Kit-8 proliferation experiment, plasmids and siRNA transfection, pyruvic acid and lactic acid production detection, immunofluorescence staining of functional mitochondria and oxygen consumption rate and extracellular acidification rate measurement were uesd to assess the glycolytic metabolism and paclitaxel resistance in ovarian cancer cells. The expression and prognostic effect of PGAM1 in 180 ovarian cancer patients were analyzed. Results: SKOV3-TR30 cells display higher glycolytic flux and lower mitochondrial function than SKOV3 cells. Down-regulation of PGAM1 in SKOV3-TR30 cells resulted in decreased paclitaxel resistance. Up-regulation of PGAM1 in SKOV3 cells led to enhanced paclitaxel resistance. Analysis of the glycolytic flux revealed that PGAM1-mediated pyruvic acid or lactic acid production could modulate the capabilities of ovarian cancer cell resistance to paclitaxel. Our data also show high expression of PGAM1 as significantly correlated with reduced overall survival and reduced progression free survival in ovarian cancer patients. Conclusions: PGAM1 acts to promote paclitaxel resistance via pyruvic acid and/or lactate production in ovarian cancer cells. Inhibiting PGAM1 may provide a new approach to favorably alter paclitaxel resistance in ovarian cancer. |
| first_indexed | 2024-04-11T10:08:07Z |
| format | Article |
| id | doaj.art-16caacc040d5415cb47ad955f068603c |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-11T10:08:07Z |
| publishDate | 2022-09-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-16caacc040d5415cb47ad955f068603c2022-12-22T04:30:10ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-09-0127926210.31083/j.fbl2709262S2768-6701(22)00614-1PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer CellsYan Feng0Xu Zhang1Songfa Zhang2Shanshan Xu3Xiaojing Chen4Caiyun Zhou5Yongmei Xi6Xing Xie7Weiguo Lu8Women's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, ChinaDepartment of Gynecology, The first Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, Zhejiang, ChinaWomen's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, ChinaWomen's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, ChinaWomen's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, ChinaWomen's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, ChinaWomen's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, ChinaWomen's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, ChinaWomen's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, ChinaBackground: Enhanced glycolysis occurs in most human cancer cells and is related to chemoresistance. However, detailed mechanisms remain vague. Methods: Using proteinomics analysis, we found that the glycolytic enzyme Phosphoglycerate mutase 1 (PGAM1) was highly expressed in the paclitaxel-resistant ovarian cancer cell line SKOV3-TR30, as compared to its parental cell line SKOV3. Cell Counting Kit-8 proliferation experiment, plasmids and siRNA transfection, pyruvic acid and lactic acid production detection, immunofluorescence staining of functional mitochondria and oxygen consumption rate and extracellular acidification rate measurement were uesd to assess the glycolytic metabolism and paclitaxel resistance in ovarian cancer cells. The expression and prognostic effect of PGAM1 in 180 ovarian cancer patients were analyzed. Results: SKOV3-TR30 cells display higher glycolytic flux and lower mitochondrial function than SKOV3 cells. Down-regulation of PGAM1 in SKOV3-TR30 cells resulted in decreased paclitaxel resistance. Up-regulation of PGAM1 in SKOV3 cells led to enhanced paclitaxel resistance. Analysis of the glycolytic flux revealed that PGAM1-mediated pyruvic acid or lactic acid production could modulate the capabilities of ovarian cancer cell resistance to paclitaxel. Our data also show high expression of PGAM1 as significantly correlated with reduced overall survival and reduced progression free survival in ovarian cancer patients. Conclusions: PGAM1 acts to promote paclitaxel resistance via pyruvic acid and/or lactate production in ovarian cancer cells. Inhibiting PGAM1 may provide a new approach to favorably alter paclitaxel resistance in ovarian cancer.https://www.imrpress.com/journal/FBL/27/9/10.31083/j.fbl2709262phosphoglycerate mutase 1paclitaxel resistanceglycolysispyruvateovarian cancer cell |
| spellingShingle | Yan Feng Xu Zhang Songfa Zhang Shanshan Xu Xiaojing Chen Caiyun Zhou Yongmei Xi Xing Xie Weiguo Lu PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells Frontiers in Bioscience-Landmark phosphoglycerate mutase 1 paclitaxel resistance glycolysis pyruvate ovarian cancer cell |
| title | PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells |
| title_full | PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells |
| title_fullStr | PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells |
| title_full_unstemmed | PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells |
| title_short | PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells |
| title_sort | pgam1 promotes glycolytic metabolism and paclitaxel resistance via pyruvic acid production in ovarian cancer cells |
| topic | phosphoglycerate mutase 1 paclitaxel resistance glycolysis pyruvate ovarian cancer cell |
| url | https://www.imrpress.com/journal/FBL/27/9/10.31083/j.fbl2709262 |
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