Figure 7. Graphical summary. HOXB9 promotes migration and invasion of NSCLC cells by inducing EMT, allowing them to break away from the primary bulk tumor and invade the surrounding capillaries. After reaching the cerebral circulation, the cells are arrested at the BBB, where degradation of junctional proteins (TJ and AJ) occurs due to release of MMP9 by tumor cells in a HOXB9-dependent manner. This results in BBB breakdown, tumor cell invasion, and establishment of brain metastasis.