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Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Letter to the Editor

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

Authors: Joana Figueiredo, Soraia Melo, Kimberley Gamet, Tanis Godwin, Susana Seixas, João M. Sanches, Parry Guilford, Raquel Seruca

Published in: Molecular Cancer | Issue 1/2018

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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.
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Metadata
Title
E-cadherin signal sequence disruption: a novel mechanism underlying hereditary cancer
Authors
Joana Figueiredo
Soraia Melo
Kimberley Gamet
Tanis Godwin
Susana Seixas
João M. Sanches
Parry Guilford
Raquel Seruca
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0859-0

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