biostudies-literatureWu Cthe General Program of the Beijing Natural Science Foundation20https://www.ebi.ac.uk/biostudies/studies/S-EPMC12908302biostudies-literatureUnknown15(1)The tumor microenvironment (TME) has a profound influence on the progression of lung adenocarcinoma (LUAD) and its response to therapy. We identified a tumor-promoting communication network based on single-cell RNA sequencing. This shows an SPP1 + macrophage and basal epithelial cell communication module (CIM) that is enriched in invasive portions of tumors, and spatially associated with decreased cytotoxic T cell activity and poor prognosis. Transcriptomic modeling identified FAM117A as a major suppressor of the CIM network. FAM117A is a DYRK1A-interacting cell-cycle regulator. Loss of FAM117A resulted in longer G1/S transition time, increased cell proliferation, and an enhanced macrophage-epithelial feedback loop. Immunohistochemical studies showed decreased FAM117A expression in LUAD tiExperimental hematology & oncologySingle-cell profiling reveals FAM117A as a key regulator linking macrophage-epithelial crosstalk with the progression of lung adenocarcinoma.PMC129083027232164Liu HHu YLi DRen ZChe GTao HWu CHou XWang JfalseSingle-cell profiling reveals FAM117A as a key regulator linking macrophage-epithelial crosstalk with the progression of lung adenocarcinoma.The tumor microenvironment (TME) has a profound influence on the progression of lung adenocarcinoma (LUAD) and its response to therapy. We identified a tumor-promoting communication network based on single-cell RNA sequencing. This shows an SPP1 + macrophage and basal epithelial cell communication module (CIM) that is enriched in invasive portions of tumors, and spatially associated with decreased cytotoxic T cell activity and poor prognosis. Transcriptomic modeling identified FAM117A as a major suppressor of the CIM network. FAM117A is a DYRK1A-interacting cell-cycle regulator. Loss of FAM117A resulted in longer G1/S transition time, increased cell proliferation, and an enhanced macrophage-epithelial feedback loop. Immunohistochemical studies showed decreased FAM117A expression in LUAD ti2026-01-01T00:00:00Z2026 Feb2026-07-16T05:05:15.792Z2026-07-09T10:38:01.166ZS-EPMC129083024169282310.1186/s40164-026-00745-9