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Review
.2023 May 11;11(5):1428.
doi: 10.3390/biomedicines11051428.

The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation

Affiliations
Review

The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation

Mimmo Turano et al. Biomedicines..

Abstract

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.

Keywords: colorectal cancers (CRCs); epithelial to mesenchymal transition (EMT); metabolic reprogramming; succinate; succinate dehydrogenase (SDH).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Approximate frequencies of each CRC molecular subtype. The main features of each molecular subtype are indicated.
Figure 2
Figure 2
Role of SDH alterations and succinate accumulation in the activation of the EMT process in CRCs. SDH alterations cause succinate accumulation and activate EMT in CRCs through at least 3 ways: (1) inhibiting PHD and thereby stabilizing HIF1-α; (2) inhibiting the TET enzyme and thus generating DNA methylation alterations; (3) causing alterations of the ETC and accumulation of ROS, which, again, stabilizes HIF1-α. HIF1-α (hypoxia-inducible factor 1-alpha); TRAP1 (TNF receptor associated protein 1); SDH (succinate dehydrogenase); PHDs (prolyl hydroxylase domain enzymes); TET (ten-eleven translocation (TET) methylcytosine dioxygenases); ROS (reactive oxygen species); EMT (epithelial–mesenchymal transition); VDACs (voltage-dependent anion-selective channel proteins); SLC25 (solute carrier family 25 members).
Figure 3
Figure 3
Extrinsic pathways activated by succinate. Succinate, secreted by tumor cells, binds its specific receptor SUCNR1 on target cells, such as endothelial cells, macrophages and other tumor cells, to induce EMT, angiogenesis and inflammatory pathways. HIF1-α (hypoxia-inducible factor 1 subunit alpha); SDH (succinate dehydrogenase); PI3Ks (phosphoinositide 3-kinases); AKT (protein kinase B, PKB); ERK (extracellular signal-regulated kinase); STAT3 (signal transducer and activator of transcription 3); VEGF (vascular endothelial growth factor); IL-1R (interleukin-1 receptor); IL-1β (interleukin-1 beta); IL-6 (interleukin-6); IL-6R (interleukin 6 receptor); SUCNR1 (succinate receptor 1); ROS (reactive oxygen species); EMT (epithelial–mesenchymal transition).
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References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. De Rosa M., Pace U., Rega D., Costabile V., Duraturo F., Izzo P., Delrio P. Genetics, diagnosis and management of colorectal cancer. Oncol. Rep. 2015;34:1087–1096. doi: 10.3892/or.2015.4108. - DOI - PMC - PubMed
    1. Turano M., Delrio P., Rega D., Cammarota F., Polverino A., Duraturo F., Izzo P., De Rosa M. Promising Colorectal Cancer Biomarkers for Precision Prevention and Therapy. Cancers. 2019;11:1932. doi: 10.3390/cancers11121932. - DOI - PMC - PubMed
    1. De Rosa M., Rega D., Costabile V., Duraturo F., Niglio A., Izzo P., Pace U., Delrio P. The biological complexity of colorectal cancer: Insights into biomarkers for early detection and personalized care. Therap. Adv. Gastroenterol. 2016;9:861–886. doi: 10.1177/1756283X16659790. - DOI - PMC - PubMed
    1. Ong B.A., Vega K.J., Houchen C.W. Intestinal stem cells and the colorectal cancer microenvironment. World. J. Gastroenterol. 2014;20:1898–1909. doi: 10.3748/wjg.v20.i8.1898. - DOI - PMC - PubMed

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