Rab37-mediated OPN secretion enriches SPP1⁺ macrophages through autocrine-paracrine signaling to drive lung tumor progression.

ABSTRACT: Tumor-associated Macrophages (TAMs) are highly plastic immune cells that shape the tumor microenvironment (TME) and influence cancer progression. However, the molecular determinants governing their functional heterogeneity remain incompletely understood. In this study, we identify Rab37 as a key regulator that remodels the states of macrophages within the lung TME. Single-cell RNA sequencing revealed that Rab37 wild-type (WT) tumors were enriched in immunosuppressive Spp1⁺ TAMs, whereas Rab37 knockout (KO) tumors contained a higher proportion of Thbs1⁺ TAMs, suggesting Rab37-dependent shifts in macrophage programming. Mechanistically, Rab37 promoted osteopontin (OPN) secretion, which activated STAT3 signaling to establish an autocrine feedback loop that sustained Spp1

SUBMITTER: Yang YE 

PROVIDER: S-EPMC12823564 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature