SASH1 inhibits proliferation and invasion of thyroid cancer cells through PI3K/Akt signaling pathway

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12276-83. eCollection 2015.

Abstract

The SASH1 (SAM- and SH3-domain containing 1) gene, a member of the SLY-family of signal adapter proteins, has an important regulatory role in tumorigenesis, but its implication in thyroid carcinoma has not been yet investigated. In this study, we investigated the role of SASH1 in proliferation and invasion of thyroid cancer cells and the underlying mechanism. Our results demonstrated that SASH1 is down-regulated in thyroid cancer cells. Overexpression of SASH1 inhibits thyroid cancer cell proliferation, migration and invasion with decreased epithelial-mesenchymal transition (EMT). Mechanistically, overexpression of SASH1 inhibits thyroid cancer cell proliferation and invasion through down-regulation of PI3K and Akt phosphorylation. Taken together, the present study showed that the loss or inhibition of SASH1 expression may play an important role in thyroid cancer development, invasion, and metastasis and that SASH1 may be a potential therapeutic target for the treatment of thyroid cancer.

Keywords: SASH1; invasion; proliferation; thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Epithelial-Mesenchymal Transition
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Signal Transduction*
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / pathology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • SASH1 protein, human
  • Tumor Suppressor Proteins
  • Phosphatidylinositol 3-Kinases