Hugl-1 inhibits glioma cell growth in intracranial model

J Neurooncol. 2015 Oct;125(1):113-21. doi: 10.1007/s11060-015-1901-3. Epub 2015 Sep 4.

Abstract

Drosophila lethal (2) giant larvae (lgl) has been reported as a tumor suppressor and could regulate the Drosophila hippo signaling. Human giant larvae-1(Hugl-1), one human homologue of Drosophila lgl, also has been reported to be involved in the development of some human cancers. However, whether Hugl-1 is associated with the pathogenesis of malignant gliomas remains poorly understood. In the present work, we examined the effect of Hugl-1 on glioma cell growth both in vitro and in vivo. Firstly, we found that Hugl-1 protein levels decreased in the human glioma tissues, suggesting that Hugl-1 is involved in glioma progression. Unfortunately, either stably or transiently over-expressing Hugl-1 did not affect glioma cell proliferation in vitro. In addition, Hugl-1 over-expression did not regulate hippo signaling pathway. Interestingly, over-expression of Hugl-1 not only inhibited gliomagenesis but also markedly inhibited cell proliferation and promoted the apoptosis of U251 cells in an orthotopic model of nude mice. Taken together, this study provides the evidence that Hugl-1 inhibits glioma cell growth in intracranial model of nude mice, suggesting that Hugl-1 might be a potential tumor target for glioma therapy.

Keywords: Gliomas; Hippo; Hugl-1; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytoma / pathology*
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Mice, Nude
  • Phenylurea Compounds / metabolism
  • Sincalide / metabolism
  • Transfection

Substances

  • Cytoskeletal Proteins
  • Ki-67 Antigen
  • LLGL1 protein, human
  • Phenylurea Compounds
  • Green Fluorescent Proteins
  • ethylene diurea
  • Sincalide