The Interaction Between Epigenetic Changes, EMT, and Exosomes in Predicting Metastasis of Colorectal Cancers (CRC)

Yang, Mon-Yuan; Sun, Mingjun; Zhang, Huijing

doi:10.3389/fonc.2022.879848

Cited by 8 publications

(5 citation statements)

References 174 publications

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“…Furthermore, higher ratio of p-FAK/FAK at early stage in the capsaicin and cold exposure groups indicates a higher degree of FAK activation, which may induce early EMT events. CRC metastasis depends on early EMT events, during which colorectal epithelial cells lose connectivity and apical base polarity to gain phenotypic capacity for mesenchymal migration and invasion 43 . EMT may be an early event involved in metastasis, as some cancer cells may acquire the ability to spread and metastasize before turning malignant 44 .…”

Section: Discussionmentioning

confidence: 99%

Capsaicin and Cold exposure promote EMT-mediated premetastatic niche formation to facilitate colorectal cancer metastasis

Nong,

Xing

2024

J. Cancer

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Colorectal cancer (CRC) is a common malignant tumor worldwide. Capsaicin and cold exposure were positively correlated with CRC metastasis. However, the mechanisms of action underlying capsaicin and cold exposure in 1,2-dimethylhyrazine (DMH)-induced CRC remain unknown. Multiple assays were utilized in the present study, including methylene blue, hematoxylin eosin (H&E) and immunohistochemistry (IHC) staining, western blotting and Duolink proximity ligation assay (PLA), in order to assess the influence of capsaicin and cold exposure on CRC rat models induced by DMH. The present study reported that capsaicin and cold exposure treatment significantly increased the size and number of colonic tumors, and the CRC metastasis rate in the capsaicin and cold exposure groups was higher than that in DMH model group.Moreover, it was observed that capsaicin and cold exposure increased mRNA and protein expression levels of LAMC2 and integrin-β1 induced by DMH. Duolink PLA results indicated that cold exposure and capsaicin significantly promoted interaction formation between LAMC2 and ITGB1 in CRC rats induced by DMH. Furthermore, western blot and IHC analysis confirmed that cold exposure and capsaicin inhibited DMH-induced decreases in the expression levels of E-cadherin, and increases in the expression levels of p-FAK, Snails, Fibronectin and N-cadherin. In addition, the serum levels of IL-1β and IL-6 in capsaicin and cold exposure group were higher than those of model group. In conclusion, our study suggests that both capsaicin and cold exposure may contribute to EMT-mediated the formation of premetastatic niche, which may lead to CRC metastasis by activating the early interaction between LAMC2 and integrin-β1.

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Section: Discussionmentioning

confidence: 99%

Capsaicin and Cold exposure promote EMT-mediated premetastatic niche formation to facilitate colorectal cancer metastasis

Nong,

Xing

2024

J. Cancer

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“…EMT is also an important mechanism for the development of chemoresistance in CRC, indicating a decrease in adhesion factors such as epithelial surface calmodulin, detachment from basement membrane connections, and cytoskeletal and morphological convergence to mesenchymal features. Various molecules such as COP9 signalosome subunit 8, runt-related transcription factor 1, ubiquitin specific peptidase 43, histone deacetylase 2 and tumor microenvironment-associated fibroblasts can regulate EMT in CRC cells ( 89 ). When EMT occurs, the malignant phenotype of intestinal cancer becomes more prominent and resistant to OXA and 5-FU ( 90 ).…”

Section: Mechanisms Of Chemoresistance In Crc Involving Key M6a Methy...mentioning

confidence: 99%

Targeting key RNA methylation enzymes to improve the outcome of colorectal cancer chemotherapy (Review)

Shao,

Han,

Huang

et al. 2023

Int J Oncol

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RNA methylation modifications are closely linked to tumor development, migration, invasion and responses to various therapies. Recent studies have shown notable advancements regarding the roles of RNA methylation in tumor immunotherapy, the tumor microenvironment and metabolic reprogramming. However, research on the association between tumor chemoresistance and N6-methyladenosine (m6A) methyltransferases in specific cancer types is still scarce. Colorectal cancer (CRC) is among the most common gastrointestinal cancers worldwide. Conventional chemotherapy remains the predominant treatment modality for CRC and chemotherapy resistance is the primary cause of treatment failure. The expression levels of m6A methyltransferases, including methyltransferase-like 3 (METTL3), METTL14 and METTL16, in CRC tissue samples are associated with patients' clinical outcomes and chemotherapy efficacy. Natural pharmaceutical ingredients, such as quercetin, have the potential to act as METTL3 inhibitors to combat chemotherapy resistance in patients with CRC. The present review discussed the various roles of different types of key RNA methylation enzymes in the development of CRC, focusing on the mechanisms associated with chemotherapy resistance. The progress in the development of certain inhibitors is also listed. The potential of using natural remedies to develop antitumor medications that target m6A methylation is also outlined.

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“…EV-mediated intracellular communication plays a role not only in maintaining cell homeostasis, but also in disease progression [ 96 , 97 , 98 , 99 ]. Exosomes are associated with several diseases, including cancer metastasis, which is the invasion and spread of primary cancer cells into other organs [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 ]. Exosomes have been shown to play an important role in the formation of the cancer microenvironment and the mechanisms of cancer malignancy, such as cancer cell growth, infiltration, metastasis, and pre-metastasis niche [ 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ].…”

Section: Evs In Cancer Metastasis and Malignant Transformationmentioning

confidence: 99%

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

Matsuzaka

Yashiro

2022

IJMS

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Extracellular vesicles (EVs), including exosomes, mediate intercellular communication by delivering their contents, such as nucleic acids, proteins, and lipids, to distant target cells. EVs play a role in the progression of several diseases. In particular, programmed death-ligand 1 (PD-L1) levels in exosomes are associated with cancer progression. Furthermore, exosomes are being used for new drug-delivery systems by modifying their membrane peptides to promote their intracellular transduction via micropinocytosis. In this review, we aim to show that an efficient drug-delivery system and a useful therapeutic strategy can be established by controlling the molecular docking and intracellular translocation of exosomes. We summarise the mechanisms of molecular docking of exosomes, the biological effects of exosomes transmitted into target cells, and the current state of exosomes as drug delivery systems.

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The Interaction Between Epigenetic Changes, EMT, and Exosomes in Predicting Metastasis of Colorectal Cancers (CRC)

Cited by 8 publications

References 174 publications

Capsaicin and Cold exposure promote EMT-mediated premetastatic niche formation to facilitate colorectal cancer metastasis

Capsaicin and Cold exposure promote EMT-mediated premetastatic niche formation to facilitate colorectal cancer metastasis

Targeting key RNA methylation enzymes to improve the outcome of colorectal cancer chemotherapy (Review)

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

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