Group I p21 activated kinases regulate thyroid cancer cell migration and are overexpressed and activated in thyroid cancer invasion.

p21 activated kinases (PAKs) are a family of serine/ threonine kinases that regulate cytoskeletal dynamics and cell motility. PAKs are subdivided into Group I (PAKs 1-3) and Group 2 (PAKs 4-6) on the basis of structural and functional characteristics. Based on prior gene expression data that predicted enhanced PAK signaling in the invasive fronts of aggressive papillary thyroid cancers (PTCs), we hypothesized that PAKs functionally regulate thyroid cancer cell motility and are activated in PTC invasive fronts. We examined PAK isoform expression in six human thyroid cancer cell lines (BCPAP, KTC1, TPC1, FTC133, C643, and SW1746) by quantitative RT-PCR and Western blot. All cell lines expressed PAKs 1-4 and 6 mRNA and PAKs 1-4 protein; PAK6 protein was variably expressed. Samples from normal and malignant thyroid tissues also expressed PAK1-4 and 6 mRNA; Transfection with the Group I (PAKs 1-3) PAK-specific p21 inhibitory domain (PID) molecular inhibitor reduced transwell filter migration by ~ 50% without altering viability in all cell lines (p