PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities
The last few decades have witnessed an advancement in our understanding of multiple cancer cell pathways related to metabolic reprogramming. One of the most important cancer hallmarks, including aerobic glycolysis (the Warburg effect), the central carbon pathway, and multiple-branch metabolic pathwa...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-01-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S235230422200054X |
| _version_ | 1797701718346039296 |
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| author | Jin Xiang Kai Wang Ni Tang |
| author_facet | Jin Xiang Kai Wang Ni Tang |
| author_sort | Jin Xiang |
| collection | DOAJ |
| description | The last few decades have witnessed an advancement in our understanding of multiple cancer cell pathways related to metabolic reprogramming. One of the most important cancer hallmarks, including aerobic glycolysis (the Warburg effect), the central carbon pathway, and multiple-branch metabolic pathway remodeling, enables tumor growth, progression, and metastasis. Phosphoenolpyruvate carboxykinase 1 (PCK1), a key rate-limiting enzyme in gluconeogenesis, catalyzes the conversion of oxaloacetate to phosphoenolpyruvate. PCK1 expression in gluconeogenic tissues is tightly regulated during fasting. In tumor cells, PCK1 is regulated in a cell-autonomous manner rather than by hormones or nutrients in the extracellular environment. Interestingly, PCK1 has an anti-oncogenic role in gluconeogenic organs (the liver and kidneys), but a tumor-promoting role in cancers arising from non-gluconeogenic organs. Recent studies have revealed that PCK1 has metabolic and non-metabolic roles in multiple signaling networks linking metabolic and oncogenic pathways. Aberrant PCK1 expression results in the activation of oncogenic pathways, accompanied by metabolic reprogramming, to maintain tumorigenesis. In this review, we summarize the mechanisms underlying PCK1 expression and regulation, and clarify the crosstalk between aberrant PCK1 expression, metabolic rewiring, and signaling pathway activation. In addition, we highlight the clinical relevance of PCK1 and its value as a putative cancer therapeutic target. |
| first_indexed | 2024-03-12T04:40:43Z |
| format | Article |
| id | doaj.art-1fb94494a942442b97c4e022423f7153 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T04:40:43Z |
| publishDate | 2023-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-1fb94494a942442b97c4e022423f71532023-09-03T09:42:40ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-01-01101101112PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunitiesJin Xiang0Kai Wang1Ni Tang2Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaCorresponding author.; Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaCorresponding author. Fax: +86 23 68486780.; Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaThe last few decades have witnessed an advancement in our understanding of multiple cancer cell pathways related to metabolic reprogramming. One of the most important cancer hallmarks, including aerobic glycolysis (the Warburg effect), the central carbon pathway, and multiple-branch metabolic pathway remodeling, enables tumor growth, progression, and metastasis. Phosphoenolpyruvate carboxykinase 1 (PCK1), a key rate-limiting enzyme in gluconeogenesis, catalyzes the conversion of oxaloacetate to phosphoenolpyruvate. PCK1 expression in gluconeogenic tissues is tightly regulated during fasting. In tumor cells, PCK1 is regulated in a cell-autonomous manner rather than by hormones or nutrients in the extracellular environment. Interestingly, PCK1 has an anti-oncogenic role in gluconeogenic organs (the liver and kidneys), but a tumor-promoting role in cancers arising from non-gluconeogenic organs. Recent studies have revealed that PCK1 has metabolic and non-metabolic roles in multiple signaling networks linking metabolic and oncogenic pathways. Aberrant PCK1 expression results in the activation of oncogenic pathways, accompanied by metabolic reprogramming, to maintain tumorigenesis. In this review, we summarize the mechanisms underlying PCK1 expression and regulation, and clarify the crosstalk between aberrant PCK1 expression, metabolic rewiring, and signaling pathway activation. In addition, we highlight the clinical relevance of PCK1 and its value as a putative cancer therapeutic target.http://www.sciencedirect.com/science/article/pii/S235230422200054XGluconeogenesisMetabolismOncogenesisPCK1Tumor |
| spellingShingle | Jin Xiang Kai Wang Ni Tang PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities Genes and Diseases Gluconeogenesis Metabolism Oncogenesis PCK1 Tumor |
| title | PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities |
| title_full | PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities |
| title_fullStr | PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities |
| title_full_unstemmed | PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities |
| title_short | PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities |
| title_sort | pck1 dysregulation in cancer metabolic reprogramming oncogenic activation and therapeutic opportunities |
| topic | Gluconeogenesis Metabolism Oncogenesis PCK1 Tumor |
| url | http://www.sciencedirect.com/science/article/pii/S235230422200054X |
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