Abstract 2042: Low Slit2 expression is associated with the aggressiveness of papillary thyroid carcinoma

Abstract

Abstract Context: Slits, representative axon guidance molecules, and their Roundabout (Robo) transmembrane receptors are identified as key regulators of many cancers. One genome-wide liknage analysis suggested Slit-Robo Rho GTPase activating protein 1 gene as a candidate gene in papillary thyroid carcinoma (PTC) susceptibility. Objective: To identify the role of Slit-Robo signaling in PTC. Results : Slits(Slit 1-3) and Robos (Robo 1-4) were expressed in all of thyroid cancer cells and Slit2, Slit3, Robo1 and Robo4 presented higher expression than others. The mRNA expression of Slits and Robos was higher in fresh frozen PTC tissues than matched normal tissues. When we conducted immunohistochemical staining of Slit2 and Robo1 in thyroid tissues, the positivity of Slit2 and Robo1 were higher in PTC tissues than benign or normal tissues. However, negative Slit2 expression was significantly associated with cervical lymph node (LN) metastasis, distant metastasis and cervical recurrence of PTC (P <.001) irrespective of BRAF mutation status. In cellular assays, Slit2 treatment inhibited proliferation of thyroid cancer cells as dose dependent manner and also significantly suppressed cell migration by inhibiting activation of beta-catenin and inducing E-cadherin. Slit2 treatment also significantly suppressed beta-catenin activation induced by Wnt3A in luciferase reporter assay. Conclusions : Low expression of Slit2 was associated with poor prognostic factors in PTC. This present study demonstrated the potential of Slit2 as a novel prognostic and therapeutic factor in PTC. Citation Format: MinJi Jeon, Won Gu Kim, Seonhee Lim, Eun Kyung Jang, Tae Yong Kim, Young Kee Shong, Won Bae Kim. Low Slit2 expression is associated with the aggressiveness of papillary thyroid carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2042. doi:10.1158/1538-7445.AM2015-2042