Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity

Biochem Biophys Res Commun. 2016 Apr 22;473(1):212-218. doi: 10.1016/j.bbrc.2016.03.081. Epub 2016 Mar 19.

Abstract

Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.

Keywords: Aurora kinase; Cell motility; Cofilin-1; Metastasis; Papillary thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Aurora Kinase A / metabolism*
  • Carcinoma / metabolism
  • Carcinoma, Papillary
  • Cell Line, Tumor
  • Cell Movement
  • Cofilin 1 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / pathology
  • Piperazines / chemistry
  • RNA, Small Interfering / metabolism
  • Regression Analysis
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Tissue Array Analysis

Substances

  • CFL1 protein, human
  • Cfl1 protein, mouse
  • Cofilin 1
  • Piperazines
  • RNA, Small Interfering
  • tozasertib
  • AURKA protein, human
  • Aurka protein, mouse
  • Aurora Kinase A