Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy
Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC pro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/4/1070 |
| _version_ | 1797621919720144896 |
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| author | Hafiza Padinharayil Vikrant Rai Alex George |
| author_facet | Hafiza Padinharayil Vikrant Rai Alex George |
| author_sort | Hafiza Padinharayil |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells’ potential to produce ATP as energy, despite retaining the redox potential optimum, and allocating materials for biosynthetic activities that are crucial for cell growth, survival, and proliferation, are assisted by mitochondria. The polyclonal tumor cells with different metabolic profiles may add to carcinogenesis through inter-metabolic coupling. Cancer cells frequently possess alterations in the mitochondrial genome, although they do not hinder metabolism; alternatively, they change bioenergetics. This can further impart retrograde signaling, educate cell signaling, epigenetic modifications, chromatin structures, and transcription machinery, and ultimately satisfy cancer cellular and nuclear demands. To maximize the tumor microenvironment (TME), tumor cells remodel nearby stromal cells and extracellular matrix. These changes initiate polyclonality, which is crucial for growth, stress response, and metastasis. Here, we evaluate all the intrinsic and extrinsic pathways drawn by mitochondria in carcinogenesis, emphasizing the perspectives of mitochondrial metabolism in PDAC progression and treatment. |
| first_indexed | 2024-03-11T09:02:52Z |
| format | Article |
| id | doaj.art-418133ccacbd4002b13f2b0637c87722 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T09:02:52Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-418133ccacbd4002b13f2b0637c877222023-11-16T19:35:43ZengMDPI AGCancers2072-66942023-02-01154107010.3390/cancers15041070Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to TherapyHafiza Padinharayil0Vikrant Rai1Alex George2Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur 680005, Kerala, IndiaDepartment of Translational Research, Western University of Health Sciences, Pomona, CA 91766-1854, USAJubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur 680005, Kerala, IndiaPancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells’ potential to produce ATP as energy, despite retaining the redox potential optimum, and allocating materials for biosynthetic activities that are crucial for cell growth, survival, and proliferation, are assisted by mitochondria. The polyclonal tumor cells with different metabolic profiles may add to carcinogenesis through inter-metabolic coupling. Cancer cells frequently possess alterations in the mitochondrial genome, although they do not hinder metabolism; alternatively, they change bioenergetics. This can further impart retrograde signaling, educate cell signaling, epigenetic modifications, chromatin structures, and transcription machinery, and ultimately satisfy cancer cellular and nuclear demands. To maximize the tumor microenvironment (TME), tumor cells remodel nearby stromal cells and extracellular matrix. These changes initiate polyclonality, which is crucial for growth, stress response, and metastasis. Here, we evaluate all the intrinsic and extrinsic pathways drawn by mitochondria in carcinogenesis, emphasizing the perspectives of mitochondrial metabolism in PDAC progression and treatment.https://www.mdpi.com/2072-6694/15/4/1070pancreatic ductal adenocarcinomamitochondriametabolismretrograde signalingextracellular matriximmune cells |
| spellingShingle | Hafiza Padinharayil Vikrant Rai Alex George Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy Cancers pancreatic ductal adenocarcinoma mitochondria metabolism retrograde signaling extracellular matrix immune cells |
| title | Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy |
| title_full | Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy |
| title_fullStr | Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy |
| title_full_unstemmed | Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy |
| title_short | Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy |
| title_sort | mitochondrial metabolism in pancreatic ductal adenocarcinoma from mechanism based perspectives to therapy |
| topic | pancreatic ductal adenocarcinoma mitochondria metabolism retrograde signaling extracellular matrix immune cells |
| url | https://www.mdpi.com/2072-6694/15/4/1070 |
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