Slap restricts oncogenic Src-family kinase signaling to maintain colonic epithelial homeostasis.

SLAP suppresses EPHB2-SFK signaling, preventing excessive colonic epithelial proliferation and tumor development, highlighting its role as a tumor suppressor in the colon.

• Why it matters: Understanding how SFK activity is restrained is crucial because unchecked SFK signaling promotes proliferation and tumorigenesis in colonic tissues, yet the mechanisms remain unclear.
• What they did: The study used epithelial-specific Slap deletion in mice and organoid models, revealing that loss of SLAP increases SFK activity, especially via the receptor EPHB2, and accelerates tumor formation.
• The result: Inhibiting EPHB2 reduced SFK activation and normalized proliferation, demonstrating SLAP’s role in constraining oncogenic signaling pathways and offering potential therapeutic targets for colonic cancer prevention.