TUSC3: functional duality of a cancer gene

Cell Mol Life Sci. 2018 Mar;75(5):849-857. doi: 10.1007/s00018-017-2660-4. Epub 2017 Sep 19.

Abstract

Two decades ago, following a systematic screening of LOH regions on chromosome 8p22, TUSC3 has been identified as a candidate tumor suppressor gene in ovarian, prostate and pancreatic cancers. Since then, a growing body of evidence documented its clinical importance in various other types of cancers, and first initial insights into its molecular function and phenotypic effects have been gained, though the precise role of TUSC3 in different cancers remains unclear. As a part of the oligosaccharyltransferase complex, TUSC3 localizes to the endoplasmic reticulum and functions in final steps of N-glycosylation of proteins, while its loss evokes the unfolded protein response. We are still trying to figure out how this mechanistic function is reconcilable with its varied effects on cancer promotion. In this review, we focus on cancer-related effects of TUSC3 and envisage a possible role of TUSC3 beyond endoplasmic reticulum.

Keywords: Cancer; Endoplasmic reticulum; Immunoediting; N-Glycosylation; Oncogene; TUSC3; Tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromosomes, Human, Pair 8
  • Endoplasmic Reticulum / metabolism*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic*
  • Genetic Loci
  • Glycosylation
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Organ Specificity
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Unfolded Protein Response

Substances

  • Membrane Proteins
  • TUSC3 protein, human
  • Tumor Suppressor Proteins