Up-Regulation of Tiam1 Promotes the Radioresistance of Laryngeal Squamous Cell Carcinoma Through Activation of the JNK/ATF-2 Signaling Pathway.

ABSTRACT

PURPOSE: Our previous study has revealed that T-lymphoma invasion and metastasis-inducing factor 1 (Tiam1) overexpression are significantly associated with aggressive behavior and poor prognosis in patients with laryngeal squamous cell carcinoma (LSCC). However, the influence of Tiam1 in the radioresistance of LSCC and its mechanism have never been elucidated. MATERIALS AND METHODS: Western blotting was used to confirm the relationship between Tiam1 and the JNK/ATF-2 signaling pathway. To explore the specific functions of Tiam1 and JNK/ATF-2 signaling pathway on the proliferation and apoptosis of LSCC after radiation, cloning formation assay and flow cytometry were conducted in vitro, and the experiments on a xenograft mouse model and TUNEL assay were performed in vivo. RESULTS: Western blotting indicated that Tiam1 can regulate the JNK/ATF-2 signaling pathway through the influence of the activity of JNK and ATF-2. Up-regulation of Tiam1 could promote proliferation and inhibit apoptosis of LSCC after radiation both in vitro and in vivo. Moreover, the down-regulation of the JNK/ATF-2 signaling pathway reduced the radioresistance of LSCC caused by Tiam1 up-regulation. CONCLUSION: These results suggest that the up-regulation of Tiam1 expression can promote the radioresistance of LSCC through activation of the JNK/ATF-2 signaling pathway.