Local soft niches in mechanically heterogeneous primary tumors promote brain metastasis via mechanotransduction-mediated HDAC3 activity.

ABSTRACT: Tumor cells with organ-specific metastasis traits arise in primary lesions with substantial variations of local niche mechanics owing to intratumoral heterogeneity. However, the roles of mechanically heterogeneous primary tumor microenvironment in metastatic organotropism remain an enigma. This study reports that persistent priming in soft but not stiff niches that mimic primary tumor mechanical heterogeneity induces transcriptional reprogramming reminiscent of neuron and promotes the acquisition of brain metastatic potential. Soft-primed cells generate brain metastases in vivo through enhanced transendothelial migration across blood-brain barrier and brain colonization, which is further supported by the findings that tumor cells residing in local soft niches of primary xenografts exhibit

SUBMITTER: Tang K 

PROVIDER: S-EPMC11864190 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature