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

Samantha K McCarty1, Motoyasu Saji, Xiaoli Zhang

  • 1Divisions of Endocrinology and Oncology Center for Biostatistics, The Ohio State University College of Medicine and Arthur G. James Comprehensive Cancer Center, 1581 Dodd Drive, Columbus, Ohio 43210, USA.

Endocrine-Related Cancer
|September 7, 2010
PubMed

Insights

p21-activated kinases (PAKs) regulate cell movement. PAK1 is particularly important for thyroid cancer cell motility and is elevated in invasive tumor fronts, suggesting it drives cancer invasion.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • p21-activated kinases (PAKs) are serine/threonine kinases crucial for cytoskeletal dynamics and cell motility.
  • PAKs are categorized into Group I (PAKs 1-3) and Group II (PAKs 4-6) based on structural and functional differences.
  • Previous gene expression data indicated heightened PAK signaling in aggressive papillary thyroid cancer (PTC) invasive fronts.

Purpose of the Study:

  • To investigate the functional role of PAKs in regulating thyroid cancer cell motility.
  • To determine if PAKs are activated in the invasive fronts of papillary thyroid cancers.
  • To examine the expression of various PAK isoforms in human thyroid cancer cell lines and tissues.

Main Methods:

  • Quantitative reverse transcription-PCR and western blot were used to assess PAK isoform expression in six human thyroid cancer cell lines.
  • PAK isoform expression was also analyzed in normal and malignant thyroid tissues.
  • Functional assays included transwell filter migration assays with PAK inhibitors and small interfering RNA (siRNA) targeting specific PAK isoforms (PAK1, PAK2, PAK3). Immunohistochemistry was performed on invasive PTC samples.

Main Results:

  • All tested thyroid cancer cell lines expressed PAKs 1-4 and PAK6 mRNA, with PAKs 1-4 protein consistently detected.
  • Inhibition of Group I PAKs significantly reduced thyroid cancer cell migration by approximately 50% without affecting cell viability.
  • PAK1-specific siRNA markedly decreased migration in BCPAP and FTC133 cells. Immunohistochemical analysis revealed increased PAK1 and phosphorylated PAK (pPAK) immunoactivity in the invasive fronts of PTCs compared to tumor centers.

Conclusions:

  • PAK isoforms are expressed in human thyroid cancer cell lines and tissues.
  • PAK1 plays a significant role in regulating thyroid cancer cell motility.
  • Elevated PAK1 and pPAK levels in PTC invasive fronts suggest PAKs are key regulators of thyroid cancer invasion.

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