P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation
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Xiaochen Xie1, Xiaoguang Shi1, Haixia Guan1, Qiqiang Guo2, Chenling Fan1, Wenwu Dong3, Guiling Wang4, Feng Li4, Zhongyan Shan1, Liu Cao2, Weiping Teng1
1Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, P.R. China
2Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang, P.R. China
3Department of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China
4Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, P.R. China
Weiping Teng, email: [email protected]
Keywords: p21-activated kinase 4, thyroid-stimulating hormone, PKA Cα, papillary thyroid cancer, cell proliferation
Received: April 21, 2016 Accepted: November 23, 2016 Published: February 04, 2017
Papillary thyroid cancer is a common endocrine malignancy. Although p21-activated kinase 4 (PAK4) is involved in the development of different types of tumor, its function has not been investigated in papillary thyroid cancer. Here, we identified a role for PAK4 in papillary thyroid cancer progression. Levels of PAK4 and PAK4 phosphorylated at serine 474 correlated significantly with tumor size and TNM stage. Furthermore, stable knockdown of PAK4 retarded cellular proliferation, migration, and invasion. Moreover, thyroid stimulating hormone-induced cellular proliferation in papillary thyroid cancer was found to be dependent on TSHR/cAMP/PKA/PAK4 signaling, with levels of phosphorylated PAK4 correlating positively with serum thyroid stimulating hormone and PKA Cα levels in patients with papillary thyroid cancer. These findings revealed a novel function of PAK4 in thyroid stimulating hormone-induced papillary thyroid cancer progression and suggest that PAK4 may become a promising diagnostic and therapeutic target for this disease.
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