SOSTDC1 inhibits follicular thyroid cancer cell proliferation, migration, and EMT via suppressing PI3K/Akt and MAPK/Erk signaling pathways

Mol Cell Biochem. 2017 Nov;435(1-2):87-95. doi: 10.1007/s11010-017-3059-0. Epub 2017 May 27.

Abstract

The sclerostin domain containing protein 1 (SOSTDC1) is a cell signaling regulator involved in cell physiology and pathology. SOSTDC1 is known to have a suppressive effect on certain kinds of cancer. However, the role of SOSTDC1 in follicular thyroid cancer (FTC) remains unknown. We aimed to investigate if the expression of SOSTDC1 plays any roles in carcinogenesis and metastasis of FTC. We found a significantly down-regulated SOSTDC1 expression in follicular thyroid cancer samples. In addition, our data showed that ectopic expression of SOSTDC1 dramatically inhibited thyroid cancer cell proliferation in vitro and in nude mice. SOSTDC1 also compromised the migratory, invasive property, and epithelial-mesenchymal transition (EMT) activity of FTC cell. Mechanically, SOSTDC1 exerted its tumor suppressor function by inhibiting the activity of major signaling pathways including the phosphatidylinositol-3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/Erk pathways. Altogether, our findings provide insight into the role of SOSTDC1 as a novel functional tumor suppressor in follicular thyroid cancer through modulating the activities of PI3K/Akt and MAPK/Erk signaling pathways.

Keywords: Cell proliferation; Follicular thyroid cancer; MAPK/Erk; Migration; PI3K/Akt; SOSTDC1.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / metabolism*
  • Adenocarcinoma, Follicular / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • MAP Kinase Signaling System*
  • Male
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SOSTDC1 protein, human
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins c-akt