Single-cell profiling reveals FAM117A as a key regulator linking macrophage-epithelial crosstalk with the progression of lung adenocarcinoma.

ABSTRACT: 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 ti

SUBMITTER: Wu C 

PROVIDER: S-EPMC12908302 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature