Cell communication analysis identified PPIA-BSG and APP-CD74 as key axes in brain and lymph node metastases, while FN1-Integrin and CTLA4-CD86 dominated in bone and adrenal metastases, respectively.<h4>Conclusions</h4>In summary, this study highlights the functional heterogeneity and site-specific interactions of cells in lung cancer metastases, providing insights into the mechanisms shaping metastatic niches and potential therapeutic strategies. Here, APP is linked to lung cancer.