High Expression of WWP1 Associates with Tumor Progression in Papillary Thyroid Cancer

Cancer Biother Radiopharm. 2022 May;37(4):313-323. doi: 10.1089/cbr.2020.4148. Epub 2021 Aug 12.

Abstract

Background: WWP1 (WW domain-containing E3 ubiquitin protein ligase 1) is increased in several kinds of carcinomas, but the influence of WWP1 in papillary thyroid cancer (PTC) is not well understood. Materials and Methods: The expression of WWP1 in PTC tissues and cells was detected by real-time reverse transcription PCR. The biological role of WWP1 on PTC cell growth, apoptosis, migration, and invasion ability was assessed with the Cell Counting Kit-8, colony forming, flow cytometry, wound healing, and transwell assays, respectively. Results: The expression of WWP1 mRNA and protein is increased in PTC tissue samples and cells. There is close correlation between the up expression of WWP1 and clinical parameters, such as tumor size, TNM, and distant metastasis. Knockdown of WWP1 blocks cell proliferation, migration, and invasion, causes cell cycle arrest, and induces apoptosis in PTC cells. Knockdown of WWP1 increases PTEN level and reduces p-PI3K and p-Akt level in PTC cells. Conclusions: Knockdown of WWP1 suppressed cell proliferation, migration, and invasion of PTC cell by downregulating the expression of p-PI3K and p-Akt, contributing to their understanding the pathogenesis of PTC.

Keywords: PTEN-Akt signaling pathway; WWP1; papillary thyroid cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology
  • Ubiquitin-Protein Ligases* / genetics

Substances

  • WWP1 protein, human
  • Ubiquitin-Protein Ligases
  • Proto-Oncogene Proteins c-akt