Targeting the JAK-STAT pathway in colorectal cancer: mechanisms, clinical implications, and therapeutic potential

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Nov. 26, 2024

Colorectal cancer (CRC) remains one of the most prevalent and fatal malignancies worldwide, consistently ranking among top three in terms incidence mortality. Despite notable advancements early detection therapeutic interventions, survival outcomes for advanced-stage CRC are still dismal, largely due to issues such as drug resistance metastasis. Recent research has increasingly implicated JAK-STAT signaling pathway a pivotal contributor pathogenesis. This evolutionarily conserved plays key role transmitting extracellular signals nucleus, thereby modulating gene expression involved numerous fundamental biological processes. In CRC, dysregulation is frequently observed strongly associated with tumor progression, including processes cellular proliferation, apoptosis, metastasis, immune evasion, sustenance stem cells. Given its integral advancement, gained recognition viable target. Extensive evidence from preclinical clinical models supports efficacy safety targeting components pathway, presenting new possibilities patients particularly addressing enhancing treatment outcomes. review offers detailed exploration focusing on regulatory mechanisms CRC-related malignancies. Moreover, it examines association between protein expression, features, prognosis, potential management.

Language: Английский

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PLXNB1/SEMA4D signals mediate interactions between malignant epithelial and immune cells to promote colorectal cancer liver metastasis

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(20)

Published: Oct. 1, 2024

Abstract Distal metastases result from metastatic microenvironment and tumour epithelial cell interactions, the cellular heterogeneity of primary colorectal cancer (CRC) liver (LM) was evaluated by integrating single‐cell sequencing data, collected gene expression data subsets used to construct a prognostic model identify intercellular receptor‐ligand interactions between immune cells in CRC LM. Multiplex immunofluorescence staining, vitro wound healing, migration apoptosis assays were performed further explore biological relevance identified potential regulatory molecules. In this study, approximately 17 subtypes detected, with Epi‐11 being highly expressed LM tissues compared samples. Furthermore, patients high metastasis‐related genetic profile had poorer prognosis. By predicting receptor–ligand found interact more myeloid T/natural killer when samples, which mediated PLXNB1/SEMA4D axis. addition, SEMA4D correlated decreased overall survival CRC, whereas PLXNB1 not. knockdown prevented promoted HCT116 vitro. summary, cells, an important subset may drive act crosstalk through signalling

Language: Английский

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Natural compounds modulate the mechanism of action of tumour-associated macrophages against colorectal cancer: a review

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(11)

Published: Nov. 15, 2024

Colorectal cancer (CRC) exhibits a substantial morbidity and mortality rate, with its aetiology pathogenesis remain elusive. It holds significant importance within the tumour microenvironment (TME) exerts crucial regulatory influence on tumorigenesis, progression, metastasis. TAMs possess capability to foster CRC pathogenesis, proliferation, invasion, metastasis, as well angiogenesis, immune evasion, resistance. Furthermore, can mediate prognosis of CRC. In this paper, we review mechanisms by which natural compounds target exert anti-CRC effects from perspective promotional CRC, mainly regulating polarization TAMs, reducing infiltration recruitment enhancing phagocytosis macrophages, signalling pathways cytokines, discuss potential value therapeutic strategies compounds-targeting pathway in clinical treatment.

Language: Английский

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Stromal cell-expressed malignant gene patterns contribute to the progression of squamous cell carcinomas across different sites

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: July 12, 2024

Background Squamous cell carcinomas (SCCs) across different anatomical locations possess common molecular features. Recent studies showed that stromal cells may contribute to tumor progression and metastasis of SCCs. Limited by current sequencing technology analysis methods, it has been difficult combine stroma expression profiles with a large number clinical information. Methods With the help transfer learning on line, single-cell, bulk data, we identified validated 2 malignant gene patterns (V1 V5) expressed SCCs from head neck (HNSCC), lung (LUSC), cervix (CESC), esophagus, breast. Results Pattern V5 reflected novel feature explained mixed signals HNSCC subtypes. Higher pattern was related shorter PFI gender cancer-type specificity. The other V1 associated poor in patients after surgery all three squamous cancer types (HNSCC p = 0.0055, LUSC 0.0292, CESC 0.0451). Cancer-associated fibroblasts could induce express V1. Adjuvant radiotherapy weaken effect high recurrence metastasis, depending radiosensitivity. Conclusion Considering prognostic value its universality, suggest genetic subtype classification be improved new system integrates both non-malignant components.

Language: Английский

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Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

The liver is an important metastatic organ that contains many innate immune cells, yet little known about their role in anti-metastatic defense. We investigated how invariant natural killer T (iNKT) cells influence colorectal cancer-derived metastasis using different models immunocompetent mice. found hepatic iNKT promote by creating a supportive niche for disseminated cancer cells. Mechanistically, respond to disseminating producing the fibrogenic cytokines IL-4 and IL-13 TCR-independent manner. Selective abrogation of sensing stellate prevented transdifferentiation into extracellular matrix-producing myofibroblasts, which hindered outgrowth This study highlights novel tumor-promoting axis driven initial stages metastasis.

Language: Английский

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