Post transcriptional control restrains the IL17–GCSF axis and limits neutrophil-driven breast cancer metastasis

Inflammatory cues remodel the tumor secretome, yet how stress coupled translational control in the tumor niche programs this intercellular communication remains unclear. Although translational control has been studied mainly as a cell autonomous driver of tumor growth, chronic inflammation, hypoxia and nutrient limitation impose endoplasmic reticulum (ER) stress that can rewire translation of secreted factors and thereby tumor–immune crosstalk. Here we show that Cytoplasmic polyadenylation element‐binding protein 4 (CPEB4) integrates pro-inflammatory environmental stress cues into mRNA stabilization in tumor cells establishing a negative feedback branch of IL 17 signaling. Ribosome profiling and RIP seq define two IL 17 regulated mRNA classes: a feedback limiting module that is bound by and requires CPEB4 for cytoplasmic polyadenylation, stability and translation, and a CPEB4 independent branch exemplified by Csf3. Loss of CPEB4 collapses the former while leaving the latter hyperactive, uncoupling post transcriptional restraint from transcriptionally linked outputs. This shift elevates tumor derived G CSF, drives systemic neutrophilia and accelerates pre metastatic niche maturation and lung metastasis in a breast cancer model. Our data establish CPEB4 as a post transcriptional rheostat that shapes tumor–immune crosstalk and suggest a novel strategy for targeting the IL 17–G CSF axis for metastasis prone breast cancer.