Single-cell and bulk transcriptomics reveal Fusobacterium nucleatum promotes colorectal cancer metastasis by upregulating LAMC2 in in vitro and in vivo models.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Fusobacterium nucleatum (F. nucleatum) has been strongly implicated in CRC metastasis. However, the contribution of laminin γ2 chain (LAMC2) to F. nucleatum-induced CRC metastasis remains elusive. We investigated the role of LAMC2 in F. nucleatum-induced CRC cell migration through a series of in vitro assays, including transmission electron microscopy, wound-healing, and transwell migration experiments, as well as in vivo animal models. Additionally, we explored the expression profile of LAMC2 in CRC tissues and assessed its prognostic relevance using immunohistochemistry, bulk transcriptome, and single-cell transcriptomics analyses. We found that F. nucleatum upregulates LAMC2 expression, thereby promoting CRC cell migration. Mechanistic analyses revealed that F. nucleatum downregulates hsa-miRNA-7977, releasing its transcriptional repression of LAMC2. Additionally, LAMC2 activates the FAK-PI3K-AKT signaling pathway and modulates H3K27 histone acetylation. Immunohistochemistry, together with single-cell and bulk transcriptome analyses, demonstrated that LAMC2 is highly expressed in metastatic CRC tissues, and is significantly associated with poor prognosis. Moreover, a Cox regression-based prognostic model constructed using LAMC2-associated genes exhibited robust predictive performance across multiple independent cohorts. Our findings identify LAMC2 as a key mediator of F. nucleatum-induced CRC metastasis and highlight it as both a prognostic biomarker and a potential therapeutic target.