62 Colorectal cancer 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 colorectal cancer remains poor. Increasing evidence suggests that inflammatory signalling within the tumour microenvironment plays a pivotal role in cancer progression, yet the molecular mechanisms linking immune cell-derived cytokines to colorectal cancer metastasis remain incompletely understood. In a recent study published in Genes and Diseases, researchers from Chongqing Medical University uncovered a signalling network through which monocyte-derived interleukin 1β (IL1β) promotes colorectal cancer progression. Combining analyses of patient samples, public datasets, in vitro functional studies, and in vivo mouse models, the investigators demonstrated that IL1β, secreted predominantly by tumour-associated monocytes, activates a p65-KRT7-ILK positive feedback loop that drives epithelial–mesenchymal transition (EMT), tumour growth, and metastasis. Initial analyses revealed that IL1β expression was significantly elevated in colorectal cancer tissues compared with adjacent normal tissues and was strongly associated with larger tumour size, increased tumour 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 IL1β within the tumour microenvironment, highlighting their critical contribution to disease progression. Mechanistically, IL1β activated NF-κB signalling by promoting phosphorylation and nuclear translocation of p65. Activated p65 subsequently enhanced transcription of KRT7, a keratin family protein previously implicated in tumour 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 IL1β signalling. Further investigation showed that KRT7 interacts with ITGA1 to activate integrin-linked kinase (ILK), triggering EMT characterised by increased expression of N-cadherin and vimentin, reduced E-cadherin expression, enhanced invadopodia formation, and greater migratory and invasive capacity in colorectal cancer cells. ILK, in turn, phosphorylated p65 at Ser536, reinforcing its nuclear localisation and sustaining KRT7 expression. This created a positive feedback loop that amplified inflammatory signalling and continuously drove aggressive tumour behaviour. Disrupting IL1β signalling with the IL1 receptor antagonist anakinra significantly reduced colorectal cancer cell proliferation, invasion, migration, and EMT, while suppressing tumour growth and liver metastasis in patient-derived xenograft and spleen-to-liver metastasis mouse models. Conversely, exogenous IL1β accelerated tumour progression both in vitro and in vivo. The study identifies monocyte-secreted IL1β as a central regulator of colorectal cancer progression through activation of the p65–KRT7–ILK signalling circuit. By revealing how inflammatory cues from the tumour microenvironment sustain EMT and metastatic potential, the findings position IL1β and its downstream signalling components as promising prognostic biomarkers and therapeutic targets for precision treatment of colorectal cancer. The work underscores the importance of targeting inflammatory pathways in the tumour microenvironment to improve outcomes for patients with advanced disease.