Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential

Entezari, Ariana A; Snook, Adam E.

doi:10.1080/14728222.2021.1937124

Cited by 8 publications

(10 citation statements)

References 114 publications

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“…The inability of APC to regulate the stability of β-catenin protein results in uncontrolled β-catenin nuclear signaling, leading to the activation of oncogenic genes [40]. Although the APC/β-catenin signaling pathway is an appealing target for gastrointestinal cancers, achieving therapeutic effects with drug interventions targeting these molecules proves to be challenging [39].…”

Section: Discussionmentioning

confidence: 99%

“…These hormones activate GC-C, setting off a cascade of downstream signaling pathways. These pathways play a pivotal role in regulating uid and electrolyte homeostasis, maintaining the integrity of the intestinal epithelium, and in uencing tumorigenesis [39].…”

Section: Discussionmentioning

confidence: 99%

“…Remarkably, the connection between the GC-C signaling pathway and CRC was initially revealed through population studies, highlighting an inverse relationship between CRC prevalence and enterotoxigenic Escherichia coli (ETEC) infections [42]. ETEC infections involve heat-stable enterotoxins that produce STs, ultimately activating the GC-C signaling pathway and causing diarrhea [39]. Additionally, the GC-C signaling pathway is implicated in CRC through the depletion of intracellular ligands, guanylin and uroguanylin.…”

Section: Discussionmentioning

confidence: 99%

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Targeted Gene-Hormone Therapy of Colorectal Cancer with Guanylin Expressing Nano-system

Samadi,

Rahbarizadeh,

Nouri

et al. 2024

Preprint

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Background Addressing colorectal cancer (CRC) poses a significant challenge, demanding the precise delivery of therapeutic agents to eliminate cancer cells while minimizing impact on healthy cells. The strategic selection of therapeutic targets, the utilization of nanocarriers with optimal efficacy and low toxicity, and the development of gene constructs with controlled induction in cancer cells are crucial aspects in this pursuit. Materials and Methods This study employed a systems biology approach to comprehensively investigate the guanylin hormone-encoding gene (GUCA2A). Exploration encompassed expression patterns across tissues and single cells, clinical endpoints, methylation profiles, mutations, immune and functional analyses. Subsequently, GUCA2A was identified as a potential target for gain of function studies, leading to its amplification and cloning into gene constructs featuring both a robust CMV promoter and a cancer-specific MUC1 promoter. The succinylated PEI-9, characterized by low toxicity and high gene transfer efficiency, was then fabricated and characterized on HCT-116 cancer cells and normal Vero cell lines. Results systems biology studies revealed GUCA2A’s aberrant expression patterns, methylation variations, mutational changes as well as its remarkable association with immune engagement and poor survival outcomes in CRC. Moreover, SPEI-9 was introduced as a highly efficient and safe nanocarrier for gene delivery purposes. Additionally, in vitro studies revealed that both guanylin-expressing gene constructs exhibited potential in inhibiting cell growth and proliferation, inducing apoptosis, suppressing cell migration, and curtailing colony formation. Notably, these effects were more robust but non-specific in cancer cells treated with constructs containing the CMV general promoter, while, induction via the MUC1 promoter was more specific. Conclusion A genetic construct featuring the strong universal CMV and specific MUC1 promoter, expressing the guanylin peptide hormone, demonstrated highly effective and specific anticancer effects when transfected with nanocarriers characterized by high efficiency and low cytotoxicity. This nano-system holds promising implications for targeted CRC therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Targeted Gene-Hormone Therapy of Colorectal Cancer with Guanylin Expressing Nano-system

Samadi,

Rahbarizadeh,

Nouri

et al. 2024

Preprint

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“…Carcinoembryonic antigen (CEA) and melanoma-associated antigen (MAGE) are the first TAAs ever identified and widely explored in the clinical trials of CRC vaccine (16). Other TAAs targeted for CRC treatment include mucin 1 (MUC-1), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 1 and 2 (VEGFR1, VEGFR2), transmembrane 4 superfamily member 5 protein (TM4SF5), survivin, mitotic centromere-associated kinesin (MCAK), guanylyl cyclase C (GUCY2C), and 5T4 (17)(18)(19)(20).…”

Section: Tumor-associated Antigenmentioning

confidence: 99%

Colorectal cancer vaccines: The current scenario and future prospects

et al. 2022

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Colorectal cancer (CRC) is one of the most common cancers worldwide. Current therapies such as surgery, chemotherapy, and radiotherapy encounter obstacles in preventing metastasis of CRC even when applied in combination. Immune checkpoint inhibitors depict limited effects due to the limited cases of CRC patients with high microsatellite instability (MSI-H). Cancer vaccines are designed to trigger the elevation of tumor-infiltrated lymphocytes, resulting in the intense response of the immune system to tumor antigens. This review briefly summarizes different categories of CRC vaccines, demonstrates the current outcomes of relevant clinical trials, and provides particular focus on recent advances on nanovaccines and neoantigen vaccines, representing the trend and emphasis of CRC vaccine development.

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“…When GUCY2C signaling is blocked, it may lead to the pathogenesis of CRC. However, GUCY2C is expressed in both human primary and metastatic CRC, and GUCY2C is considered to be a tumor marker ( 35 ). GUCY2C is highly expressed in 95% of CRC metastasis ( 36 ).…”

Section: Basic Experimental Of Car-t Cells Therapy For Crcmentioning

confidence: 99%

Recent advances in CAR-T cells therapy for colorectal cancer

Qin

Chen

et al. 2022

Front. Immunol.

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Colorectal cancer (CRC) is the third most common cancer, with a high mortality rate and a serious impact on people’s life and health. In recent years, adoptive chimeric antigen receptor T (CAR-T) cells therapy has shown well efficacy in the treatment of hematological malignancies, but there are still many problems and challenges in solid tumors such as CRC. For example, the tumor immunosuppressive microenvironment, the low targeting of CAR-T cells, the short time of CAR-T cells in vivo, and the limited proliferation capacity of CAR-T cells, CAR-T cells can not effectively infiltrate into the tumor and so on. New approaches have been proposed to address these challenges in CRC, and this review provides a comprehensive overview of the current state of CAR-T cells therapy in CRC.

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Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential

Cited by 8 publications

References 114 publications

Targeted Gene-Hormone Therapy of Colorectal Cancer with Guanylin Expressing Nano-system

Targeted Gene-Hormone Therapy of Colorectal Cancer with Guanylin Expressing Nano-system

Colorectal cancer vaccines: The current scenario and future prospects

Recent advances in CAR-T cells therapy for colorectal cancer

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