FOXM1 in Bone Metastasis

Why FOXM1 matters in metastasis, bone biology, and possible targeting strategies in bone-metastasis research

FOXM1 is an oncogenic transcription factor and a major regulator of cancer progression.

It influences tumour growth, invasion, and spread to distant sites, including bone.

Cell cycle: drives G1 to S and G2 to M phase transitions
Invasion and migration: upregulates matrix metalloproteinases that help break down extracellular matrix
EMT: helps stationary cancer cells acquire migratory and invasive behaviour
Angiogenesis: increases VEGF expression and supports tumour blood-vessel growth
Drug resistance: higher FOXM1 expression is linked to chemotherapy and endocrine resistance in breast cancer

Its role in native bone cells is still not fully resolved.

The current picture is mixed:

its role in osteoclast differentiation remains unclear, with contradictory findings across studies
inhibiting FOXM1 may enhance osteoblast formation in some settings
in breast cancer, higher FOXM1 expression is linked to lymph-node metastasis, more aggressive phenotypes, and poorer prognosis in ER-positive disease
FOXM1 interacts with TGF-β signalling, which is already strongly linked to breast-cancer spread into bone
in prostate cancer, FOXM1 is highly expressed in bone metastases and appears to support tumour growth in skeletal sites

Several FOXM1-targeting strategies have shown preclinical interest:

Honokiol suppresses FOXM1 expression
Andrographolide lowers FOXM1 through the ROS-FOXM1-ERα axis in ER-positive breast-cancer models and also appears to reduce breast-cancer-induced osteoclast activity
TGF-β1 plus FOXM1 co-inhibition via nanoparticles is being studied preclinically for triple-negative breast cancer with bone metastasis

Human data on FOXM1-targeted strategies remains limited.

This is still an active research area rather than an established clinical strategy.

A narrative review of research progress on FoxM1 in breast cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667115/

Sustained activation of SMAD3/SMAD4 by FOXM1 promotes TGF-β-dependent cancer metastasis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904622/

TGF-β1 and FOXM1 siRNA co-loaded nanoparticles for triple-negative breast cancer and its bone metastases therapy
https://www.tandfonline.com/doi/abs/10.1080/03639045.2024.2404979

Andrographolide Inhibits ER-Positive Breast Cancer Growth and Enhances Fulvestrant Efficacy via ROS-FOXM1-ER-α Axis
https://pmc.ncbi.nlm.nih.gov/articles/PMC9124841/

FOXM1 as a novel therapeutic target for cancer drug therapy
https://pubmed.ncbi.nlm.nih.gov/25640357/

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