Slit2/Robo1 signaling inhibits small‐cell lung cancer by targeting β‐catenin signaling in tumor cells and macrophages

In patients with small‐cell lung cancer (SCLC), the expression of SLIT2 is greatly reduced, whereas the SLIT2 receptor, roundabout guidance receptor 1 (ROBO1), is significantly elevated. SLIT2 overexpression or the deletion of ROBO1 restricts tumor growth in vitro and in vivo. In addition, SLIT2 treatment enhances M1‐like phagocytic macrophages and reduces M2‐like tumor‐associated macrophages (TAMs) in SCLC tumors. This study demonstrates that the expression of the slit guidance ligand 2 (SLIT2) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue. Using genetically engineered SCLC cells, adenovirus gene therapy, and preclinical xenograft models, the study showed that SLIT2 overexpression or the deletion of ROBO1 restricts tumor growth in vitro and in vivo.