Work

A marine-derived sesterterpenoid inhibits migration and invasion of triple-negative breast cancer cells by suppressing the FAK signaling pathway

Year: 2026

Type: article

Abstract: Background: The high incidence of distant metastasis in triple-negative breast cancer (TNBC) remains the principal driver of disease-related mortality, highlighting an urgent clinical need for novel therapeutics to restrict tumor progression and dissemination. Methods: . Transcriptomic profiling and biochemical analyses were performed to elucidate the underlying signaling alterations. Results: evaluations demonstrated that MHO7 profoundly curtails MDA-MB-231 cell migration and invasion, strengthens adherens junctions, and exhibits robust primary tumor growth inhibition without inducing overt systemic toxicity in preclinical mouse models. Mechanistically, transcriptomic profiling coupled with biochemical analyses revealed that MHO7 exerts inhibitory effects on cell migration and invasion primarily by attenuating the Focal Adhesion Kinase (FAK) signaling pathway. Specifically, MHO7 treatment remarkably suppressed the autophosphorylation of FAK (Y397) and the subsequent recruitment of p-Src (Y419). This pathway suppression consequently altered cytoskeletal architecture, attenuated the downstream PI3K/AKT signaling cascade, and curtailed tumor angiogenesis. Furthermore, we identified a dual inhibitory mechanism wherein MHO7 successfully dismantled the oncogenic crosstalk between FAK and the canonical Wnt/β-catenin pathway by significantly downregulating nuclear β-catenin accumulation. Conclusion: MHO7 exerts tumor-suppressive and anti-migratory effects in TNBC primarily by attenuating FAK signaling and its downstream pathways, supporting its potential as a promising therapeutic candidate for highly aggressive TNBC.

Source: Frontiers in Cell and Developmental Biology

DOI: 10.3389/fcell.2026.1967923