The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation
Colorectal cancer (CRC) stands as the third most significant contributor to cancer-related mortality worldwide. A major underlying reason is that the detection of CRC usually occurs at an advanced metastatic stage, rendering therapies ineffective. In the progression from the in situ neoplasia stage...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/5/1428 |
| _version_ | 1827741892331175936 |
|---|---|
| author | Mimmo Turano Rosario Vicidomini Francesca Cammarota Valeria D’Agostino Francesca Duraturo Paola Izzo Marina De Rosa |
| author_facet | Mimmo Turano Rosario Vicidomini Francesca Cammarota Valeria D’Agostino Francesca Duraturo Paola Izzo Marina De Rosa |
| author_sort | Mimmo Turano |
| collection | DOAJ |
| description | Colorectal cancer (CRC) stands as the third most significant contributor to cancer-related mortality worldwide. A major underlying reason is that the detection of CRC usually occurs at an advanced metastatic stage, rendering therapies ineffective. In the progression from the in situ neoplasia stage to the advanced metastatic stage, a critical molecular mechanism involved is the epithelial-to-mesenchymal transition (EMT). This intricate transformation consists of a series of molecular changes, ultimately leading the epithelial cell to relinquish its features and acquire mesenchymal and stem-like cell characteristics. The EMT regulation involves several factors, such as transcription factors, cytokines, micro RNAs and long noncoding RNAs. Nevertheless, recent studies have illuminated an emerging link between metabolic alterations and EMT in various types of cancers, including colorectal cancers. In this review, we delved into the pivotal role played by EMT during CRC progression, with a focus on highlighting the relationship between the alterations of the tricarboxylic acid cycle, specifically those involving the succinate dehydrogenase enzyme, and the activation of the EMT program. In fact, emerging evidence supports the idea that elucidating the metabolic modifications that can either induce or inhibit tumor progression could be of immense significance for shaping new therapeutic approaches and preventative measures. We conclude that an extensive effort must be directed towards research for the standardization of drugs that specifically target proteins such as SDH and SUCNR1, but also TRAP1, PDH, ERK1/2, STAT3 and the HIF1-α catabolism. |
| first_indexed | 2024-03-11T03:54:33Z |
| format | Article |
| id | doaj.art-393cbc8f06484e9c96f41a50059ff7a3 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T03:54:33Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-393cbc8f06484e9c96f41a50059ff7a32023-11-18T00:36:57ZengMDPI AGBiomedicines2227-90592023-05-01115142810.3390/biomedicines11051428The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate AccumulationMimmo Turano0Rosario Vicidomini1Francesca Cammarota2Valeria D’Agostino3Francesca Duraturo4Paola Izzo5Marina De Rosa6Department of Biology, University of Naples Federico II, 80126 Naples, ItalySection on Cellular Communication, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USADepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, ItalyColorectal cancer (CRC) stands as the third most significant contributor to cancer-related mortality worldwide. A major underlying reason is that the detection of CRC usually occurs at an advanced metastatic stage, rendering therapies ineffective. In the progression from the in situ neoplasia stage to the advanced metastatic stage, a critical molecular mechanism involved is the epithelial-to-mesenchymal transition (EMT). This intricate transformation consists of a series of molecular changes, ultimately leading the epithelial cell to relinquish its features and acquire mesenchymal and stem-like cell characteristics. The EMT regulation involves several factors, such as transcription factors, cytokines, micro RNAs and long noncoding RNAs. Nevertheless, recent studies have illuminated an emerging link between metabolic alterations and EMT in various types of cancers, including colorectal cancers. In this review, we delved into the pivotal role played by EMT during CRC progression, with a focus on highlighting the relationship between the alterations of the tricarboxylic acid cycle, specifically those involving the succinate dehydrogenase enzyme, and the activation of the EMT program. In fact, emerging evidence supports the idea that elucidating the metabolic modifications that can either induce or inhibit tumor progression could be of immense significance for shaping new therapeutic approaches and preventative measures. We conclude that an extensive effort must be directed towards research for the standardization of drugs that specifically target proteins such as SDH and SUCNR1, but also TRAP1, PDH, ERK1/2, STAT3 and the HIF1-α catabolism.https://www.mdpi.com/2227-9059/11/5/1428colorectal cancers (CRCs)epithelial to mesenchymal transition (EMT)succinate dehydrogenase (SDH)succinatemetabolic reprogramming |
| spellingShingle | Mimmo Turano Rosario Vicidomini Francesca Cammarota Valeria D’Agostino Francesca Duraturo Paola Izzo Marina De Rosa The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation Biomedicines colorectal cancers (CRCs) epithelial to mesenchymal transition (EMT) succinate dehydrogenase (SDH) succinate metabolic reprogramming |
| title | The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation |
| title_full | The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation |
| title_fullStr | The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation |
| title_full_unstemmed | The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation |
| title_short | The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation |
| title_sort | epithelial to mesenchymal transition in colorectal cancer progression the emerging role of succinate dehydrogenase alterations and succinate accumulation |
| topic | colorectal cancers (CRCs) epithelial to mesenchymal transition (EMT) succinate dehydrogenase (SDH) succinate metabolic reprogramming |
| url | https://www.mdpi.com/2227-9059/11/5/1428 |
| work_keys_str_mv | AT mimmoturano theepithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT rosariovicidomini theepithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT francescacammarota theepithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT valeriadagostino theepithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT francescaduraturo theepithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT paolaizzo theepithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT marinaderosa theepithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT mimmoturano epithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT rosariovicidomini epithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT francescacammarota epithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT valeriadagostino epithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT francescaduraturo epithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT paolaizzo epithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation AT marinaderosa epithelialtomesenchymaltransitionincolorectalcancerprogressiontheemergingroleofsuccinatedehydrogenasealterationsandsuccinateaccumulation |