P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation.
P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation.
复制标题
P21 激活激酶 4 涉及 TSH 诱导的甲状腺乳头状癌细胞增殖
DOI：
10.18632/oncotarget.15079
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发表时间：
2017-04-11
期刊：
影响因子：
--
通讯作者：
Teng W
中科院分区：
文献类型：
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作者：
Xie X;Shi X;Guan H;Guo Q;Fan C;Dong W;Wang G;Li F;Shan Z;Cao L;Teng W
甲状腺乳头状癌是一种常见的内分泌恶性肿瘤。虽然p21激活激酶4（PAK 4）参与了不同类型肿瘤的发展，但其在甲状腺乳头状癌中的功能尚未研究。在这里，我们确定了PAK 4在甲状腺乳头状癌进展中的作用。PAK 4和PAK 4丝氨酸474磷酸化水平与肿瘤大小和TNM分期显著相关。此外，PAK 4的稳定敲低延缓了细胞增殖、迁移和侵袭。此外，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/PAK 4信号传导，甲状腺乳头状癌患者中磷酸化PAK 4水平与血清甲状腺刺激素和PKA Cα水平呈正相关。这些发现揭示了PAK 4在甲状腺刺激甲状腺激素诱导的甲状腺乳头状癌进展中的新功能，并表明PAK 4可能成为该疾病的有希望的诊断和治疗靶点。
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.