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p21激活激酶4参与促甲状腺激素诱导的甲状腺乳头状癌细胞增殖。

P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation.

作者信息

Xie Xiaochen, Shi Xiaoguang, Guan Haixia, Guo Qiqiang, Fan Chenling, Dong Wenwu, Wang Guiling, Li Feng, Shan Zhongyan, Cao Liu, Teng Weiping

机构信息

Department 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.

Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang, P.R. China.

出版信息

Oncotarget. 2017 Apr 11;8(15):24882-24891. doi: 10.18632/oncotarget.15079.

DOI:10.18632/oncotarget.15079
PMID:28178642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5421896/
Abstract

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.

摘要

甲状腺乳头状癌是一种常见的内分泌恶性肿瘤。尽管p21激活激酶4（PAK4）参与不同类型肿瘤的发生发展，但其在甲状腺乳头状癌中的功能尚未得到研究。在此，我们确定了PAK4在甲状腺乳头状癌进展中的作用。PAK4及丝氨酸474磷酸化的PAK4水平与肿瘤大小和TNM分期显著相关。此外，稳定敲低PAK4可抑制细胞增殖、迁移和侵袭。而且，发现甲状腺刺激素诱导的甲状腺乳头状癌细胞增殖依赖于TSHR/cAMP/PKA/PAK4信号通路，在甲状腺乳头状癌患者中，磷酸化PAK4水平与血清甲状腺刺激素及PKA Cα水平呈正相关。这些发现揭示了PAK4在甲状腺刺激素诱导的甲状腺乳头状癌进展中的新功能，并表明PAK4可能成为该疾病有前景的诊断和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/35c6d1b29f5a/oncotarget-08-24882-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/438a32c12d35/oncotarget-08-24882-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/14a0c887a5b2/oncotarget-08-24882-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/892a97e8b821/oncotarget-08-24882-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/c946882bb5b0/oncotarget-08-24882-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/35c6d1b29f5a/oncotarget-08-24882-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/438a32c12d35/oncotarget-08-24882-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/14a0c887a5b2/oncotarget-08-24882-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/892a97e8b821/oncotarget-08-24882-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/c946882bb5b0/oncotarget-08-24882-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6367/5421896/35c6d1b29f5a/oncotarget-08-24882-g005.jpg

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