Here, our data revealed that lung cancer cells could control the levels of Dkk1 in brain metastatic cascades, leading to the shaping of the pro-tumorigenic microenvironment in different phases: a pre-metastatic niche with insensitive microglia without tumor elements, and a micro-metastatic niche characterized by the presence of active microglia and lung cancer cells. This evidence concerns the gene DKK1 and lung cancer.