A marine-derived sesterterpenoid inhibits migration and invasion of triple-negative breast cancer cells by suppressing the FAK signaling pathway
5 affiliations
- 1Department of Pharmacy, Renmin Hospital of Wuhan University , ,
- 2Department of Radiology, Renmin Hospital of Wuhan University , ,
- 3Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University , ,
- 4Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University , ,
- 5Department of Orthopedics, Renmin Hospital of Wuhan University , ,
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
We investigated the anti-tumor potential and underlying molecular mechanisms of MHO7 (6-epi-ophiobolin G), a structurally unique sesterterpenoid derived from a marine fungus, using MDA-MB-231 cells in vitro and a subcutaneous xenograft model in vivo. Transcriptomic profiling and biochemical analyses were performed to elucidate the underlying signaling alterations.Results
Both in vitro and in vivo 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.
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BibTeX
@article{wen2026marinederived,
title = {{A marine-derived sesterterpenoid inhibits migration and invasion of triple-negative breast cancer cells by suppressing the FAK signaling pathway}},
author = {Haiyan Wen and Feifei Zeng and Yu Lan and Yuping Yin and Yuxiang Huang and Yutong Hu and Jiaheng Yin and Juanjuan Li and Siqi Zhou and Kui Hong},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1967923},
url = {https://europepmc.org/article/PMC/PMC13716777},
note = {CC BY},
}
RIS
TY - JOUR
TI - A marine-derived sesterterpenoid inhibits migration and invasion of triple-negative breast cancer cells by suppressing the FAK signaling pathway
AU - Haiyan Wen
AU - Feifei Zeng
AU - Yu Lan
AU - Yuping Yin
AU - Yuxiang Huang
AU - Yutong Hu
AU - Jiaheng Yin
AU - Juanjuan Li
AU - Siqi Zhou
AU - Kui Hong
PY - 2026
DA - 2026/10/15
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1967923
UR - https://europepmc.org/article/PMC/PMC13716777
AB - 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 We investigated the anti-tumor potential and underlying molecular mechanisms of MHO7 (6-epi-ophiobolin G), a structurally unique sesterterpenoid derived from a marine fungus, using MDA-MB-231 cells in vitro and a subcutaneous xenograft model in vivo. Transcriptomic profiling and biochemical analyses were performed to elucidate the underlying signaling alterations.Results Both in vitro and in vivo 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.
SN - 2296-634X
ER -