The role of Slit2 as a tumor suppressor in thyroid cancer.

Slits, representative axon guidance molecules, and their Roundabout (Robo) transmembrane receptors play roles in the progression of many cancers. We investigated the effects of Slit2 on the proliferation, migration, and invasion of thyroid cancer cells, and on the prognosis of papillary thyroid cancer (PTC). Slit2 overexpression inhibited the proliferation, migration and invasion of thyroid cancer cells by inhibiting transcriptional activity of beta-catenin and regulating Rho GTPase activity. Slit2 knockdown activated the migration and invasion of thyroid cancer cells and transcriptional activity of beta-catenin. Fragment Slit2 treatment inhibited thyroid cancer cell proliferation in a dose dependent manner, and also inhibited migration and invasion. When we evaluated the protein expression of Slit2 in PTCs, 24 of 160 PTCs (15%) were negative for Slit2 protein expression and these patients had significantly increased risk of cervical lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and recurrence of PTC (P < 0.001). Our findings suggest a role for Slit2 as a tumor suppressor, and also as a novel prognostic and potential therapeutic target for thyroid cancer.