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Open AccessEditorial

Advances in Molecular Mechanisms of Gastrointestinal Tumors

by Shihori Tanabe

Cancers 2024, 16(8), 1603; https://doi.org/10.3390/cancers16081603 - 22 Apr 2024

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Abstract

Gastrointestinal cancer is one of the most common malignancies worldwide [...] Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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15 pages, 9356 KiB

Open AccessArticle

Possibility of Using Conventional Computed Tomography Features and Histogram Texture Analysis Parameters as Imaging Biomarkers for Preoperative Prediction of High-Risk Gastrointestinal Stromal Tumors of the Stomach

by Milica Mitrovic Jovanovic, Aleksandra Djuric Stefanovic, Dimitrije Sarac, Jelena Kovac, Aleksandra Jankovic, Dusan J. Saponjski, Boris Tadic, Milena Kostadinovic, Milan Veselinovic, Vladimir Sljukic, Ognjan Skrobic, Marjan Micev, Dragan Masulovic, Predrag Pesko and Keramatollah Ebrahimi

Cancers 2023, 15(24), 5840; https://doi.org/10.3390/cancers15245840 - 14 Dec 2023

Cited by 3 | Viewed by 1282

Abstract

Background: The objective of this study is to determine the morphological computed tomography features of the tumor and texture analysis parameters, which may be a useful diagnostic tool for the preoperative prediction of high-risk gastrointestinal stromal tumors (HR GISTs). Methods: This is a [...] Read more.

Background: The objective of this study is to determine the morphological computed tomography features of the tumor and texture analysis parameters, which may be a useful diagnostic tool for the preoperative prediction of high-risk gastrointestinal stromal tumors (HR GISTs). Methods: This is a prospective cohort study that was carried out in the period from 2019 to 2022. The study included 79 patients who underwent CT examination, texture analysis, surgical resection of a lesion that was suspicious for GIST as well as pathohistological and immunohistochemical analysis. Results: Textural analysis pointed out min norm (p = 0.032) as a histogram parameter that significantly differed between HR and LR GISTs, while min norm (p = 0.007), skewness (p = 0.035) and kurtosis (p = 0.003) showed significant differences between high-grade and low-grade tumors. Univariate regression analysis identified tumor diameter, margin appearance, growth pattern, lesion shape, structure, mucosal continuity, enlarged peri- and intra-tumoral feeding or draining vessel (EFDV) and max norm as significant predictive factors for HR GISTs. Interrupted mucosa (p < 0.001) and presence of EFDV (p < 0.001) were obtained by multivariate regression analysis as independent predictive factors of high-risk GISTs with an AUC of 0.878 (CI: 0.797–0.959), sensitivity of 94%, specificity of 77% and accuracy of 88%. Conclusion: This result shows that morphological CT features of GIST are of great importance in the prediction of non-invasive preoperative metastatic risk. The incorporation of texture analysis into basic imaging protocols may further improve the preoperative assessment of risk stratification. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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20 pages, 5237 KiB

Open AccessArticle

Synaptotagmin 1 Suppresses Colorectal Cancer Metastasis by Inhibiting ERK/MAPK Signaling-Mediated Tumor Cell Pseudopodial Formation and Migration

by Jianyun Shi, Wenjing Li, Zhenhua Jia, Ying Peng, Jiayi Hou, Ning Li, Ruijuan Meng, Wei Fu, Yanlin Feng, Lifei Wu, Lan Zhou, Deping Wang, Jing Shen, Jiasong Chang, Yanqiang Wang and Jimin Cao

Cancers 2023, 15(21), 5282; https://doi.org/10.3390/cancers15215282 - 3 Nov 2023

Cited by 2 | Viewed by 1526

Abstract

Although synaptotagmin 1 (SYT1) has been identified participating in a variety of cancers, its role in colorectal cancer (CRC) remains an enigma. This study aimed to demonstrate the effect of SYT1 on CRC metastasis and the underlying mechanism. We first found that SYT1 [...] Read more.

Although synaptotagmin 1 (SYT1) has been identified participating in a variety of cancers, its role in colorectal cancer (CRC) remains an enigma. This study aimed to demonstrate the effect of SYT1 on CRC metastasis and the underlying mechanism. We first found that SYT1 expressions in CRC tissues were lower than in normal colorectal tissues from the CRC database and collected CRC patients. In addition to this, SYT1 expression was also lower in CRC cell lines than in the normal colorectal cell line. SYT1 expression was downregulated by TGF-β (an EMT mediator) in CRC cell lines. In vitro, SYT1 overexpression repressed pseudopodial formation and reduced cell migration and invasion of CRC cells. SYT1 overexpression also suppressed CRC metastasis in tumor-bearing nude mice in vivo. Moreover, SYT1 overexpression promoted the dephosphorylation of ERK1/2 and downregulated the expressions of Slug and Vimentin, two proteins tightly associated with EMT in tumor metastasis. In conclusion, SYT1 expression is downregulated in CRC. Overexpression of SYT1 suppresses CRC cell migration, invasion, and metastasis by inhibiting ERK/MAPK signaling-mediated CRC cell pseudopodial formation. The study suggests that SYT1 is a suppressor of CRC and may have the potential to be a therapeutic target for CRC. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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21 pages, 7433 KiB

Open AccessArticle

New Insights on the Progesterone (P4) and PGRMC1/NENF Complex Interactions in Colorectal Cancer Progression

by Joanna Kamińska, Olga Martyna Koper-Lenkiewicz, Donata Ponikwicka-Tyszko, Weronika Lebiedzińska, Ewelina Palak, Maria Sztachelska, Piotr Bernaczyk, Justyna Dorf, Katarzyna Guzińska-Ustymowicz, Konrad Zaręba, Sławomir Wołczyński, Nafis Ahmed Rahman and Violetta Dymicka-Piekarska

Cancers 2023, 15(20), 5074; https://doi.org/10.3390/cancers15205074 - 20 Oct 2023

Cited by 4 | Viewed by 1583

Abstract

The literature data regarding the risk of colorectal cancer (CRC) in the context of hormone therapy (HT), including both estrogen–progestogen combinations and estrogen alone, are inconclusive. The precise relationship underlying the action of progesterone (P4) and progesterone receptors in CRC has yet to [...] Read more.

The literature data regarding the risk of colorectal cancer (CRC) in the context of hormone therapy (HT), including both estrogen–progestogen combinations and estrogen alone, are inconclusive. The precise relationship underlying the action of progesterone (P4) and progesterone receptors in CRC has yet to be determined. We characterized the expression profiles of both nuclear and membrane progesterone receptors and their potential cofactors in CRC tissues. Additionally, we analyzed the P4 and NENF treatment effects on the cell proliferation and invasion of DLD-1 and HT-29 colorectal cancer cells. We observed a weak expression of the nuclear P4 receptor (PGR), but an abundant expression of the P4 receptor membrane component 1 (PGRMC1) and neuron-derived neurotrophic factor (NENF) in the CRC tissues. P4 treatment stimulated the proliferation of the DLD-1 and HT-29 CRC cells. The co-treatment of P4 and NENF significantly increased the invasiveness of the DLD-1 and HT-29 cells. A functional analysis revealed that these effects were dependent on PGRMC1. AN immunocytochemical analysis demonstrated a cytoplasmic co-localization of PGRMC1 and NENF in the CRC cells. Moreover, the concentration of serum NENF was significantly higher in CRC patients, and P4 treatment significantly increased the release of NENF in the DLD-1 cells. P4 or NENF treatment also significantly increased the IL-8 release in the DLD-1 cells. Our data may provide novel insights into the action of P4 and PGRMC1/NENF in CRC progression, where NENF may act as a potential PGRMC1 co-activator in non-classical P4 signaling. Furthermore, NENF, as a secreted protein, potentially could serve as a promising circulating biomarker candidate for distinguishing between colorectal cancer patients and healthy individuals, although large-scale extensive studies are needed to establish this. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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16 pages, 3546 KiB

Open AccessArticle

Modulatory Properties of Aloe secundiflora’s Methanolic Extracts on Targeted Genes in Colorectal Cancer Management

by John M. Macharia, Timea Varjas, Ruth W. Mwangi, Zsolt Káposztás, Nóra Rozmann, Márton Pintér, Isabel N. Wagara and Bence L. Raposa

Cancers 2023, 15(20), 5002; https://doi.org/10.3390/cancers15205002 - 16 Oct 2023

Cited by 1 | Viewed by 1488

Abstract

Colon tumors have a very complicated and poorly understood pathogenesis. Plant-based organic compounds might provide a novel source for cancer treatment with a sufficient novel mode of action. The objective of this study was to analyze and evaluate the efficacy of Aloe secundiflora’s [...] Read more.

Colon tumors have a very complicated and poorly understood pathogenesis. Plant-based organic compounds might provide a novel source for cancer treatment with a sufficient novel mode of action. The objective of this study was to analyze and evaluate the efficacy of Aloe secundiflora’s (AS) methanolic extracts on the expression of CASPS9, 5-LOX, Bcl2, Bcl-xL, and COX-2 in colorectal cancer (CRC) management. Caco-2 cell lines were used in the experimental study. In the serial exhaustive extraction (SEE) method, methanol was utilized as the extraction solvent. Upon treatment of CASPS9 with the methanolic extracts, the expression of the genes was progressively upregulated, thus, dose-dependently increasing the rate of apoptosis. On the other hand, the expressions of 5-LOX, Bcl2, and Bcl-xL were variably downregulated in a dose-dependent manner. This is a unique novel study that evaluated the effects of AS methanolic extracts in vitro on CRC cell lines using different dosage concentrations. We, therefore, recommend the utilization of AS and the application of methanol as the extraction solvent of choice for maximum modulatory benefits in CRC management. In addition, we suggest research on the specific metabolites in AS involved in the modulatory pathways that suppress the development of CRC and potential metastases. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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17 pages, 4445 KiB

Open AccessArticle

Transcriptomic Changes Associated with ERBB2 Overexpression in Colorectal Cancer Implicate a Potential Role of the Wnt Signaling Pathway in Tumorigenesis

by Eman A. Abdul Razzaq, Khuloud Bajbouj, Amal Bouzid, Noura Alkhayyal, Rifat Hamoudi and Riyad Bendardaf

Cancers 2023, 15(1), 130; https://doi.org/10.3390/cancers15010130 - 26 Dec 2022

Cited by 4 | Viewed by 3587

Abstract

Colorectal cancer (CRC) remains the third most common cause of cancer mortality worldwide. Precision medicine using OMICs guided by transcriptomic profiling has improved disease diagnosis and prognosis by identifying many CRC targets. One such target that has been actively pursued is an erbb2 [...] Read more.

Colorectal cancer (CRC) remains the third most common cause of cancer mortality worldwide. Precision medicine using OMICs guided by transcriptomic profiling has improved disease diagnosis and prognosis by identifying many CRC targets. One such target that has been actively pursued is an erbb2 receptor tyrosine kinase 2 (ERBB2) (Human Epidermal Growth Factor Receptor 2 (HER2)), which is overexpressed in around 3–5% of patients with CRC worldwide. Despite targeted therapies against HER2 showing significant improvement in disease outcomes in multiple clinical trials, to date, no HER2-based treatment has been clinically approved for CRC. In this study we performed whole transcriptome ribonucleic acid (RNA) sequencing on 11 HER2+ and 3 HER2− CRC patients with advanced stages II, III and IV of the disease. In addition, transcriptomic profiling was carried out on CRC cell lines (HCT116 and HT29) and normal colon cell lines (CCD841 and CCD33), ectopically overexpressing ERBB2. Our analysis revealed transcriptomic changes involving many genes in both CRC cell lines overexpressing ERBB2 and in HER2+ patients, compared to normal colon cell lines and HER2− patients, respectively. Gene Set Enrichment Analysis indicated a role for HER2 in regulating CRC pathogenesis, with Wnt/β-catenin signaling being mediated via a HER2-dependent regulatory pathway impacting expression of the homeobox gene NK2 homeobox 5 (NKX2-5). Results from this study thus identified putative targets that are co-expressed with HER2 in CRC warranting further investigation into their role in CRC pathogenesis. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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15 pages, 2878 KiB

Open AccessArticle

SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors

by Elizabeth Proaño-Pérez, Eva Serrano-Candelas, Cindy Mancia, Arnau Navinés-Ferrer, Mario Guerrero and Margarita Martin

Cancers 2022, 14(24), 6198; https://doi.org/10.3390/cancers14246198 - 15 Dec 2022

Cited by 4 | Viewed by 1993

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding [...] Read more.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding Protein 2 (SH3BP2) downregulated KIT and PDGFRA and microphthalmia-associated transcription factor (MITF) levels and reduced tumor growth. This study shows that SH3BP2 silencing also decreases levels of ETV1, a required factor for GIST growth. To dissect the SH3BP2 pathway in GIST cells, we performed a miRNA array in SH3BP2-silenced GIST cell lines. Among the most up-regulated miRNAs, we found miR-1246 and miR-5100 to be predicted to target MITF and ETV1. Overexpression of these miRNAs led to a decrease in MITF and ETV1 levels. In this context, cell viability and cell cycle progression were affected, and a reduction in BCL2 and CDK2 was observed. Interestingly, overexpression of MITF enhanced cell proliferation and significantly rescued the viability of miRNA-transduced cells. Altogether, the KIT-SH3BP2-MITF/ETV1 pathway deserves to be considered in GIST cell survival and proliferation. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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18 pages, 5323 KiB

Open AccessArticle

CD155 Cooperates with PD-1/PD-L1 to Promote Proliferation of Esophageal Squamous Cancer Cells via PI3K/Akt and MAPK Signaling Pathways

by Xiyang Tang, Jie Yang, Anping Shi, Yanlu Xiong, Miaomiao Wen, Zhonglin Luo, Huanhuan Tian, Kaifu Zheng, Yujian Liu, Chen Shu, Nan Ma, Rui Wang and Jinbo Zhao

Cancers 2022, 14(22), 5610; https://doi.org/10.3390/cancers14225610 - 15 Nov 2022

Cited by 8 | Viewed by 2242

Abstract

Background: Esophageal cancer is still a leading cause of death among all tumors in males, with unsatisfactory responses to novel immunotherapies such as anti-PD-1 agents. Herein, we explored the role of CD155 in esophageal squamous cell cancer (ESCA) and its underlying molecular mechanisms. [...] Read more.

Background: Esophageal cancer is still a leading cause of death among all tumors in males, with unsatisfactory responses to novel immunotherapies such as anti-PD-1 agents. Herein, we explored the role of CD155 in esophageal squamous cell cancer (ESCA) and its underlying molecular mechanisms. Methods: Publicly available datasets were used for differential gene expression and immune infiltration analyses, and their correlation with patient survival. A total of 322 ESCA and 161 paracancer samples were collected and evaluated by performing immunohistochemistry and the H score was obtained by performing semiquantitative analysis. In vitro transfection of ESCA cell lines with lentivirus vectors targeting CD155 was performed to knockdown the protein. These cells were analyzed by conducting RNA sequencing, and the effects of CD155 knockdown on cell cycle and apoptosis were verified with flow cytometry and Western blotting. In addition, in vivo experiments using these engineered cell lines were performed to determine the role of CD155 in tumor formation. A small interfering RNA-mediated knockdown of Nectin3 was used to determine whether it phenocopied the profile of CD155 knockdown. Results: CD155 is highly expressed in ESCA tissues and is positively associated with PD1, PDL1, CD4, IL2RA, and S100A9 expression. Furthermore, CD155 knockdown inhibited ESCA cells’ proliferation by impairing the cell cycle and inducing cell apoptosis. Bioinformatics analysis of the gene expression profile of these engineered cells showed that CD155 mainly contributed to the regulation of PI3K/Akt and MAPK signals. The downregulation of Nectin3 expression phenocopied the profile of CD155 knockdown. Discussion: CD155 may cooperate with PD-1/PD-L1 to support ESCA proliferation in ways other than regulating its underlying immune mechanisms. Indeed, CD155 downregulation can impair ESCA cell pro-cancerous behavior via the inhibition of the PI3K/Akt and MAPK signaling pathways. Moreover, Nectin3 may be a ligand of CD155 and participate in the regulation of ESCA cells’ proliferation. Hence, the inhibition of CD155 may enhance the therapeutic effect of anti-PD-1 immunotherapies in ESCA. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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Review

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21 pages, 1407 KiB

Open AccessReview

Photodynamic Therapy and Immunological View in Gastrointestinal Tumors

by David Aebisher, Paweł Woźnicki, Klaudia Dynarowicz, Aleksandra Kawczyk-Krupka, Grzegorz Cieślar and Dorota Bartusik-Aebisher

Cancers 2024, 16(1), 66; https://doi.org/10.3390/cancers16010066 - 22 Dec 2023

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Abstract

Gastrointestinal cancers are a specific group of oncological diseases in which the location and nature of growth are of key importance for clinical symptoms and prognosis. At the same time, as research shows, they pose a serious threat to a patient’s life, especially [...] Read more.

Gastrointestinal cancers are a specific group of oncological diseases in which the location and nature of growth are of key importance for clinical symptoms and prognosis. At the same time, as research shows, they pose a serious threat to a patient’s life, especially at an advanced stage of development. The type of therapy used depends on the anatomical location of the cancer, its type, and the degree of progression. One of the modern forms of therapy used to treat gastrointestinal cancers is PDT, which has been approved for the treatment of esophageal cancer in the United States. Despite the increasingly rapid clinical use of this treatment method, the exact immunological mechanisms it induces in cancer cells has not yet been fully elucidated. This article presents a review of the current understanding of the mode of action of photodynamic therapy on cells of various gastrointestinal cancers with an emphasis on colorectal cancer. The types of cell death induced by PDT include apoptosis, necrosis, and pyroptosis. Anticancer effects are also a result of the destruction of tumor vasculature and activation of the immune system. Many reports exist that concern the mechanism of apoptosis induction, of which the mitochondrial pathway is most often emphasized. Photodynamic therapy may also have a beneficial effect on such aspects of cancer as the ability to develop metastases or contribute to reducing resistance to known pharmacological agents. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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18 pages, 1433 KiB

Open AccessReview

Harnessing Ferroptosis to Overcome Drug Resistance in Colorectal Cancer: Promising Therapeutic Approaches

by Xiaofei Cheng, Feng Zhao, Bingxin Ke, Dong Chen and Fanlong Liu

Cancers 2023, 15(21), 5209; https://doi.org/10.3390/cancers15215209 - 30 Oct 2023

Cited by 7 | Viewed by 2574

Abstract

Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming [...] Read more.

Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming drug resistance in CRC. This review examines the role of ferroptosis in CRC and its impact on drug resistance. It highlights the distinctive features and advantages of ferroptosis compared to other cell death pathways, such as apoptosis and necrosis. Furthermore, the review discusses current research advances in the field, including novel treatment approaches that target ferroptosis. These approaches involve the use of ferroptosis inducers, interventions in iron metabolism and lipid peroxidation, and combination therapies to enhance the efficacy of ferroptosis. The review also explores the potential of immunotherapy in modulating ferroptosis as a therapeutic strategy. Additionally, it evaluates the strengths and limitations of targeting ferroptosis, such as its selectivity, low side effects, and potential to overcome resistance, as well as challenges related to treatment specificity and drug development. Looking to the future, this review discusses the prospects of ferroptosis-based therapies in CRC, emphasizing the importance of further research to elucidate the interaction between ferroptosis and drug resistance. It proposes future directions for more effective treatment strategies, including the development of new therapeutic approaches, combination therapies, and integration with emerging fields such as precision medicine. In conclusion, harnessing ferroptosis represents a promising avenue for overcoming drug resistance in CRC. Continued research efforts in this field are crucial for optimizing therapeutic outcomes and providing hope for CRC patients. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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30 pages, 3574 KiB

Open AccessReview

An Update of G-Protein-Coupled Receptor Signaling and Its Deregulation in Gastric Carcinogenesis

by Huan Yan, Jing-Ling Zhang, Kam-Tong Leung, Kwok-Wai Lo, Jun Yu, Ka-Fai To and Wei Kang

Cancers 2023, 15(3), 736; https://doi.org/10.3390/cancers15030736 - 25 Jan 2023

Cited by 1 | Viewed by 3328

Abstract

G-protein-coupled receptors (GPCRs) belong to a cell surface receptor superfamily responding to a wide range of external signals. The binding of extracellular ligands to GPCRs activates a heterotrimeric G protein and triggers the production of numerous secondary messengers, which transduce the extracellular signals [...] Read more.

G-protein-coupled receptors (GPCRs) belong to a cell surface receptor superfamily responding to a wide range of external signals. The binding of extracellular ligands to GPCRs activates a heterotrimeric G protein and triggers the production of numerous secondary messengers, which transduce the extracellular signals into cellular responses. GPCR signaling is crucial and imperative for maintaining normal tissue homeostasis. High-throughput sequencing analyses revealed the occurrence of the genetic aberrations of GPCRs and G proteins in multiple malignancies. The altered GPCRs/G proteins serve as valuable biomarkers for early diagnosis, prognostic prediction, and pharmacological targets. Furthermore, the dysregulation of GPCR signaling contributes to tumor initiation and development. In this review, we have summarized the research progress of GPCRs and highlighted their mechanisms in gastric cancer (GC). The aberrant activation of GPCRs promotes GC cell proliferation and metastasis, remodels the tumor microenvironment, and boosts immune escape. Through deep investigation, novel therapeutic strategies for targeting GPCR activation have been developed, and the final aim is to eliminate GPCR-driven gastric carcinogenesis. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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19 pages, 1935 KiB

Open AccessReview

EZH2: An Accomplice of Gastric Cancer

by Wuhan Yu, Ning Liu, Xiaogang Song, Lang Chen, Mancai Wang, Guohui Xiao, Tengfei Li, Zheyuan Wang and Youcheng Zhang

Cancers 2023, 15(2), 425; https://doi.org/10.3390/cancers15020425 - 9 Jan 2023

Cited by 12 | Viewed by 3312

Abstract

Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Understanding the factors influencing the therapeutic effects in gastric cancer patients and the molecular mechanism behind gastric cancer is still facing challenges. In addition to genetic [...] Read more.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Understanding the factors influencing the therapeutic effects in gastric cancer patients and the molecular mechanism behind gastric cancer is still facing challenges. In addition to genetic alterations and environmental factors, it has been demonstrated that epigenetic mechanisms can also induce the occurrence and progression of gastric cancer. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressor complex 2 (PRC2), which trimethylates histone 3 at Lys-27 and regulates the expression of downstream target genes through epigenetic mechanisms. It has been found that EZH2 is overexpressed in the stomach, which promotes the progression of gastric cancer through multiple pathways. In addition, targeted inhibition of EZH2 expression can effectively delay the progression of gastric cancer and improve its resistance to chemotherapeutic agents. Given the many effects of EZH2 in gastric cancer, there are no studies to comprehensively describe this mechanism. Therefore, in this review, we first introduce EZH2 and clarify the mechanisms of abnormal expression of EZH2 in cancer. Secondly, we summarize the role of EZH2 in gastric cancer, which includes the association of the EZH2 gene with genetic susceptibility to GC, the correlation of the EZH2 gene with gastric carcinogenesis and invasive metastasis, the resistance to chemotherapeutic drugs of gastric cancer mediated by EZH2 and the high expression of EZH2 leading to poor prognosis of gastric cancer patients. Finally, we also clarify some of the current statuses of drug development regarding targeted inhibition of EZH2/PRC2 activity. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Gastrointestinal Tumors)

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