p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1
Altered lipid metabolism is a hallmark of cancer. p73, a p53 family member, regulates cellular processes and is expressed as multiple isoforms. However, the role of p73 in regulating lipid metabolism is not well-characterized. Previously, we found that loss of p73 exon 12 (<i>E12</i>) le...
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MDPI AG
2022-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/16/2516 |
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| author | Zachary Rabow Kyra Laubach Xiangmudong Kong Tong Shen Shakur Mohibi Jin Zhang Oliver Fiehn Xinbin Chen |
| author_facet | Zachary Rabow Kyra Laubach Xiangmudong Kong Tong Shen Shakur Mohibi Jin Zhang Oliver Fiehn Xinbin Chen |
| author_sort | Zachary Rabow |
| collection | DOAJ |
| description | Altered lipid metabolism is a hallmark of cancer. p73, a p53 family member, regulates cellular processes and is expressed as multiple isoforms. However, the role of p73 in regulating lipid metabolism is not well-characterized. Previously, we found that loss of p73 exon 12 (<i>E12</i>) leads to an isoform switch from p73α to p73α1, the latter of which has strong tumor suppressive activity. In this study, comprehensive untargeted metabolomics was performed to determine whether p73α1 alters lipid metabolism in non-small cell lung carcinoma cells. RNA-seq and molecular biology approaches were combined to identify lipid metabolism genes altered upon loss of <i>E12</i> and identify a direct target of p73α1. We found that loss of <i>E12</i> leads to decreased levels of phosphatidylcholines, and this was due to decreased expression of genes involved in phosphatidylcholine synthesis. Additionally, we found that E12-knockout cells had increased levels of phosphatidylcholines containing saturated fatty acids (FAs) and decreased levels of phosphatidylcholines containing monounsaturated fatty acids (MUFAs). We then found that p73α1 inhibits cancer cell viability through direct transcriptional suppression of Stearoyl-CoA Desaturase-1 (SCD1), which converts saturated FAs to MUFAs. Finally, we showed that p73α1-mediated suppression of SCD1 leads to increased ratios of saturated FAs to MUFAs. |
| first_indexed | 2024-03-09T13:41:27Z |
| format | Article |
| id | doaj.art-83b2b5ee08cd4db5b966da33b2891c24 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T13:41:27Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-83b2b5ee08cd4db5b966da33b2891c242023-11-30T21:06:36ZengMDPI AGCells2073-44092022-08-011116251610.3390/cells11162516p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1Zachary Rabow0Kyra Laubach1Xiangmudong Kong2Tong Shen3Shakur Mohibi4Jin Zhang5Oliver Fiehn6Xinbin Chen7West Coast Metabolomics Center, University of California, Davis, CA 95616, USAComparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, CA 95616, USAComparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, CA 95616, USAWest Coast Metabolomics Center, University of California, Davis, CA 95616, USAComparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, CA 95616, USAComparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, CA 95616, USAWest Coast Metabolomics Center, University of California, Davis, CA 95616, USAComparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, CA 95616, USAAltered lipid metabolism is a hallmark of cancer. p73, a p53 family member, regulates cellular processes and is expressed as multiple isoforms. However, the role of p73 in regulating lipid metabolism is not well-characterized. Previously, we found that loss of p73 exon 12 (<i>E12</i>) leads to an isoform switch from p73α to p73α1, the latter of which has strong tumor suppressive activity. In this study, comprehensive untargeted metabolomics was performed to determine whether p73α1 alters lipid metabolism in non-small cell lung carcinoma cells. RNA-seq and molecular biology approaches were combined to identify lipid metabolism genes altered upon loss of <i>E12</i> and identify a direct target of p73α1. We found that loss of <i>E12</i> leads to decreased levels of phosphatidylcholines, and this was due to decreased expression of genes involved in phosphatidylcholine synthesis. Additionally, we found that E12-knockout cells had increased levels of phosphatidylcholines containing saturated fatty acids (FAs) and decreased levels of phosphatidylcholines containing monounsaturated fatty acids (MUFAs). We then found that p73α1 inhibits cancer cell viability through direct transcriptional suppression of Stearoyl-CoA Desaturase-1 (SCD1), which converts saturated FAs to MUFAs. Finally, we showed that p73α1-mediated suppression of SCD1 leads to increased ratios of saturated FAs to MUFAs.https://www.mdpi.com/2073-4409/11/16/2516p73 isoformsthe p53 familyStearoyl-CoA Desaturaselipid metabolismKennedy pathway |
| spellingShingle | Zachary Rabow Kyra Laubach Xiangmudong Kong Tong Shen Shakur Mohibi Jin Zhang Oliver Fiehn Xinbin Chen p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1 Cells p73 isoforms the p53 family Stearoyl-CoA Desaturase lipid metabolism Kennedy pathway |
| title | p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1 |
| title_full | p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1 |
| title_fullStr | p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1 |
| title_full_unstemmed | p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1 |
| title_short | p73α1, an Isoform of the p73 Tumor Suppressor, Modulates Lipid Metabolism and Cancer Cell Growth via Stearoyl-CoA Desaturase-1 |
| title_sort | p73α1 an isoform of the p73 tumor suppressor modulates lipid metabolism and cancer cell growth via stearoyl coa desaturase 1 |
| topic | p73 isoforms the p53 family Stearoyl-CoA Desaturase lipid metabolism Kennedy pathway |
| url | https://www.mdpi.com/2073-4409/11/16/2516 |
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