P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation.
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.
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.
Xiaochen
X
Xie
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.
Xiaoguang
X
Shi
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.
Haixia
H
Guan
Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang, P.R. China.
Qiqiang
Q
Guo
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.
Chenling
C
Fan
Department of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Wenwu
W
Dong
Department 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.
Guiling
G
Wang
Department 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.
Feng
F
Li
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.
Zhongyan
Z
Shan
Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang, P.R. China.
Liu
L
Cao
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.
Weiping
W
Teng
D000293:Adolescent; D000328:Adult; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D011989:Receptors, Thyrotropin / Q000378:metabolism; D015398:Signal Transduction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism*; D055815:Young Adult; D054462:p21-Activated Kinases / Q000378:metabolism*
D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000242:Cyclic AMP; C116367:PAK4 protein, human; D054462:p21-Activated Kinases; D017868:Cyclic AMP-Dependent Protein Kinases
PKA Cα; cell proliferation; p21-activated kinase 4; papillary thyroid cancer; thyroid-stimulating hormone