Исследователи выявили механизм, через который воспаление стимулирует метастазирование рака толстой кишки

Colorectal cancer (CRC) remains one of the most common and lethal malignancies worldwide, with metastatic disease accounting for the majority of cancer-related deaths. Although advances in screening and targeted therapies have improved patient outcomes, the prognosis for recurrent and metastatic CRC remains poor. Increasing evidence suggests that inflammatory signaling within the tumor microenvironment plays a pivotal role in cancer progression, yet the molecular mechanisms linking immune cell-derived cytokines to CRC metastasis remain incompletely understood. In a recent study published in Genes & Diseases, researchers from Chongqing Medical University uncovered a signaling network through which monocyte-derived interleukin-1β (IL-1β) promotes CRC progression. Combining analyses of patient samples, public datasets, in vitro functional studies, and in vivo mouse models, the investigators demonstrated that IL-1β secreted predominantly by tumor-associated monocytes activates a p65–KRT7–ILK positive feedback loop that drives epithelial–mesenchymal transition (EMT), tumor growth, and metastasis. Initial analyses revealed that IL-1β expression was significantly elevated in CRC tissues compared with adjacent normal tissues and was strongly associated with larger tumor size, increased tumor invasion, lymph node metastasis, and poor patient prognosis. Single-cell transcriptomic analysis, immunofluorescence, flow cytometry, PCR, and Western blotting consistently identified monocytes as the primary source of IL-1β within the tumor microenvironment, highlighting their critical contribution to CRC progression. Mechanistically, IL-1β activated NF-κB signaling by promoting phosphorylation and nuclear translocation of p65. Activated p65 subsequently enhanced transcription of KRT7, a keratin family protein previously implicated in tumor invasion and metastasis. Functional genomic analyses, including CUT&Tag and luciferase reporter assays, confirmed that p65 directly binds the KRT7 promoter, establishing KRT7 as a downstream transcriptional target of IL-1β signaling. Further investigation demonstrated that KRT7 interacts with ITGA1 to activate integrin-linked kinase (ILK), triggering EMT characterized by increased expression of N-cadherin and vimentin, reduced E-cadherin expression, enhanced invadopodia formation, and increased migratory and invasive capabilities of CRC cells. Importantly, ILK further phosphorylated p65 at Ser536, reinforcing its nuclear localization and sustaining KRT7 expression. This positive feedback loop amplified inflammatory signaling and continuously promoted aggressive tumor behavior. Functional experiments showed that disrupting IL-1β signaling with the IL-1 receptor antagonist anakinra significantly reduced CRC cell proliferation, invasion, migration, and EMT, while suppressing tumor growth and liver metastasis in patient-derived xenograft and spleen-to-liver metastasis mouse models. Conversely, exogenous IL-1β accelerated tumor progression both in vitro and in vivo. Overall, this study identifies monocyte-secreted IL-1β as a central regulator of CRC progression through activation of the p65–KRT7–ILK signaling circuit. By revealing how inflammatory cues from the tumor microenvironment sustain EMT and metastatic potential, these findings establish IL-1β and its downstream signaling components as promising prognostic biomarkers and therapeutic targets for precision treatment of CRC. Reference Title of Original Paper: Monocyte secretory IL-1β promotes colorectal cancer epithelial–mesenchymal transition via the p65–KRT7–ILK feedback Journal: Genes & Diseases Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch. DOI: https://doi.org/10.1016/j.gendis.2026.102250