Affordable Access

Access to the full text

E-cadherin signal sequence disruption: a novel mechanism underlying hereditary cancer

Authors
  • Figueiredo, Joana1, 2
  • Melo, Soraia1, 2, 3
  • Gamet, Kimberley4
  • Godwin, Tanis5
  • Seixas, Susana1, 2
  • Sanches, João M.6
  • Guilford, Parry5
  • Seruca, Raquel1, 2, 3
  • 1 Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal , Porto (Portugal)
  • 2 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal , Porto (Portugal)
  • 3 Medical Faculty of the University of Porto, Porto, Portugal , Porto (Portugal)
  • 4 Genetic Health Service NZ, Auckland City Hospital, Auckland, New Zealand , Auckland (New Zealand)
  • 5 University of Otago, Cancer Genetics Laboratory, Centre for Translational Cancer Research (Te Aho Matatū), Department of Biochemistry, Dunedin, New Zealand , Dunedin (New Zealand)
  • 6 Institute for Systems and Robotics (ISR/IST), LARSyS, Bioengineering Department, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal , Lisbon (Portugal)
Type
Published Article
Journal
Molecular Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Aug 01, 2018
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12943-018-0859-0
Source
Springer Nature
Keywords
License
Green

Abstract

The aim of this study was to uncover the pathogenic relevance and the underlying molecular mechanism of a novel CDH1 variant found in a Hereditary Diffuse Gastric Cancer family (p.L13_L15del), which affects the signal peptide of E-cadherin without changing the remaining predicted sequence. We verified that p.L13_L15del cells yield low levels of E-cadherin, decreased cell adhesion and enhanced cell invasion. Further, we demonstrated that the disruption of the highly conserved hydrophobic core of the signal peptide hampers the binding of cellular components crucial for E-cadherin translation and translocation into the endoplasmic reticulum, constituting a new molecular basis for the loss of a tumour suppressor gene causative of hereditary cancer.

Report this publication

Statistics

Seen <100 times