G2 and S phase-expressed-1 acts as a putative tumor promoter in cervical cancer by enhancing Wnt/β-catenin signaling via modulation of GSK-3β

Environ Toxicol. 2021 Aug;36(8):1628-1639. doi: 10.1002/tox.23158. Epub 2021 May 11.

Abstract

G2 and S phase-expressed-1 (GTSE1) is currently identified as a key regulator of carcinogenesis. However, the involvement of GTSE1 in cervical cancer is unclear. The aims of this work were to explore the relationship between GTSE1 and cervical cancer. Our data elucidated high GTSE1 expression in cervical cancer tissue, which predicted a poor prognosis in cervical cancer patients. GTSE1 knockdown had tumor-suppressive effects in cervical cancer cells by inhibiting cell proliferative and invasive abilities. GTSE1 knockdown decreased the level of phosphorylated glycogen synthase kinase-3β (GSK-3β) and active β-catenin, resulted in inactivation of Wnt/β-catenin signaling. Suppression of GSK-3β remarkably abolished the GTSE1-knockdown-induced inhibitory effects on Wnt/β-catenin signaling. Suppression of Wnt/β-catenin signaling abolished the GTSE1-overexpression-induced oncogenic effects. Notably, GTSE1 knockdown impeded the in vivo tumorigenicity of cervical cancer cells. In short, this work demonstrates that GTSE1 is overexpressed in cervical cancer and GTSE1 suppression exerts a tumor-inhibiting role in cervical cancer by down-regulating Wnt/β-catenin signaling. Our work underlines a crucial relevance between GTSE1 and cervical cancer progression and suggests GTSE1 as a promising therapeutic target for cervical cancer.

Keywords: GSK-3β; GTSE1; Wnt; cervical cancer.

MeSH terms

  • Carcinogens
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Microtubule-Associated Proteins
  • S Phase
  • Uterine Cervical Neoplasms*
  • beta Catenin* / metabolism

Substances

  • Carcinogens
  • GTSE1 protein, human
  • Microtubule-Associated Proteins
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta