SPI1-driven POSTN transcription promotes esophageal cancer progression and macrophage immunosuppressive polarization

Esophageal cancer (EC) is a common gastrointestinal cancer with the highest mortality. Studies have suggested that macrophages play a key role in cancer progression. Increasing evidence reveals that periostin (POSTN) is associated with the physiological and pathological processes in EC. However, the upstream mechanisms of POSTN on EC cell oncogenic properties and macrophages are still vague.

qRT-PCR and western blotting were used to detect the mRNA and protein levels. Cell survival, migration, and invasion were determined using 5-ethynyl-2'-deoxyuridine, colony formation, flow cytometry, and Transwell assays. Macrophage infiltration and polarization were detected by Transwell assay and flow cytometry. The interaction between POSTN and Salmonella pathogenicity island 1 (SPI1) was verified using ChIP and dual-luciferase reporter assays. Xenograft models were established for in vivo assay.

POSTN was highly expressed in EC tissues and cells. The knockdown of POSTN suppressed EC cell growth, migration, and invasion, as well as eliminated macrophage infiltration and M2-like polarization, but induced M1-like activation. Mechanistically, SPI1 bound directly to the promoter region of POSTN and induced POSTN transcription. SPI1 expression was also increased in EC tissues. SPI1 silencing inhibited EC cell growth, migration, and invasion, and contained macrophage infiltration and M2-like polarization, while these effects were reversed by POSTN overexpression. In vivo assay showed that POSTN overexpression abolished SPI1-induced growth inhibition in EC xenografts.

SPI1-driven POSTN transcription promotes EC cell growth and induces macrophage infiltration and immunosuppressive polarization, suggesting a new target for EC therapy.