Cell biology

Metastasis

Engineering

Neuroscience

Biology

Dormancy

Astrocyte

Cancer research

Botany

Triple-negative breast cancer

Brain metastasis

Mechanical engineering

Genetics

Laminin

Central nervous system

Dystroglycan

Cell

Limiting

Breast cancer

Cancer

Germination

Nature Cancer

Although dormancy is thought to play a key role in the metastasis of breast tumor cells to the brain, our knowledge of the molecular mechanisms regulating disseminated tumor cell (DTC) dormancy in this organ is limited. Here using serial intravital imaging of dormant and metastatic triple-negative breast cancer lines, we identify escape from the single-cell or micrometastatic state as the rate-limiting step towards brain metastasis. We show that every DTC occupies a vascular niche, with quiescent DTCs residing on astrocyte endfeet. At these sites, astrocyte-deposited laminin-211 drives DTC quiescence by inducing the dystroglycan receptor to associate with yes-associated protein, thereby sequestering it from the nucleus and preventing its prometastatic functions. These findings identify a brain-specific mechanism of DTC dormancy and highlight the need for a more thorough understanding of tumor dormancy to develop therapeutic approaches that prevent brain metastasis.

Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain