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.
Highlights
Thyroid cancer is one of the most common endocrine malignancies, with incidence rates predicted to increase by the year 2030 to make it the fourth leading cancer in terms of diagnosis [1]
The results showed that 90.8% of tumor samples and 9.2% of normal thyroid tissue samples showed positive p21activated kinase 4 (PAK4) staining, while 82.7% of tumor samples and 15.3% of normal thyroid tissue samples were positive for p-PAK4 (Table 1)
When PAK4 and p-PAK4 levels were compared between paired samples from same patients by western blotting, elevated levels of p-PAK4 and PAK4 were observed in Papillary thyroid carcinoma (PTC) samples than in their normal paired counterparts (Figures 1B and 1C)
Summary
Thyroid cancer is one of the most common endocrine malignancies, with incidence rates predicted to increase by the year 2030 to make it the fourth leading cancer in terms of diagnosis [1]. Proteins that regulate PTC development and progression may act as novel prognostic markers and have to be identified to improve prognosis. The p21-activated kinases (PAKs) belong to a conserved family of serine/threonine protein kinases. PAK4 activity can be induced in a Rho GTPasedependent or -independent manner. PAK4 phosphorylated at serine 474 (p-PAK4) is considered as the form of kinase activation [4]. Mounting evidence suggest that PAK4 expression is tightly correlated with cancer progression, which makes PAK4 a potentially promising diagnostic and therapeutic target for cancer therapy
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