Yes-associated protein 1 promotes papillary thyroid cancer cell proliferation by activating the ERK/MAPK signaling pathway

Oncotarget. 2017 Feb 14;8(7):11719-11728. doi: 10.18632/oncotarget.14319.

Abstract

Yes-associated protein 1 (YAP1) stimulates cell proliferation, epithelial-to-mesenchymal transition, invasion and metastasis in several cancers. Here, we investigated the involvement of YAP1 in papillary thyroid carcinoma (PTC) by assessing YAP1 mRNA and protein levels in PTC tissues and matched normal thyroid epithelial tissues from 50 patients. YAP1 mRNA and protein levels were higher in PTC tumor tissues than in control tissues, and correlated positively with the levels of proliferation-related genes (KI67 and c-MYC). We also used lentiviral vectors to overexpress or silence YAP1 expression in the K1 PTC cell line so that we could investigate the effects of YAP1 on cancer cell proliferation. YAP1 overexpression enhanced PTC cell proliferation by activating ERK1/2 and AKT, and these effects were impaired by treating the cells with the MEK inhibitor U0126 or the AKT inhibitor GSK690693. Finally, YAP1 overexpression dramatically induced growth of tumors from PTC cells in a xenograft mouse model. These results suggest that YAP1 enhances cell proliferation in PTC, and thus may be a promising target in the treatment of PTC.

Keywords: YAP1; papillary thyroid cancer; proliferation; signaling pathway.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Carcinoma / enzymology
  • Carcinoma / metabolism*
  • Carcinoma / pathology*
  • Carcinoma, Papillary
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Disease Models, Animal
  • Female
  • Heterografts
  • Humans
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphoproteins / metabolism*
  • Signal Transduction
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / enzymology
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology*
  • Transcription Factors
  • Transfection
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human