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

Autor: Raquel Seruca, Joao Sanches, Joana Figueiredo, Soraia Melo, Kimberley Gamet, Susana Seixas, Parry Guilford, Tanis D Godwin
Přispěvatelé: Instituto de Investigação e Inovação em Saúde
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Signal peptide
Male
Cancer Research
Chromosomal translocation
Germline variants
Endoplasmic Reticulum
CDH1
0302 clinical medicine
Cadherins / genetics
Stomach Neoplasms / metabolism
Letter to the Editor
biology
Endoplasmic Reticulum / metabolism
Translation (biology)
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Cadherins
3. Good health
Cell biology
Protein Transport
Oncology
030220 oncology & carcinogenesis
Cadherins / metabolism
Molecular Medicine
Female
Hereditary diffuse gastric cancer
Antigens
CD / genetics
Adult
Protein Sorting Signals
lcsh:RC254-282
03 medical and health sciences
Antigens
CD
Stomach Neoplasms
medicine
Cell Adhesion
Humans
Stomach Neoplasms / genetics
Cell adhesion
Cadherin
Antigens
CD / metabolism
Post-translational mechanism
Endoplasmic reticulum
E-cadherin
Genetic Variation
Sequence Analysis
DNA
medicine.disease
030104 developmental biology
Hereditary Diffuse Gastric Cancer
biology.protein
Zdroj: Molecular Cancer
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Molecular Cancer, Vol 17, Iss 1, Pp 1-7 (2018)
ISSN: 1476-4598
Popis: 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. This work was financed by FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE), Programa Operacional Regional do Norte (Norte 2020) and by National Funds through the Portuguese Foundation for Science and Technology (FCT), under the projects PTDC/BIM-ONC/0171/2012, PTDC/BIM-ONC/0281/2014, PTDC/BBB-IMG/0283/2014, NORTE-01-0145-FEDER-000029; Post-Doctoral grant SFRH/BPD/87705/2012-JF and Doctoral grant SFRH/BD/108009/2015-SM. We acknowledge the American Association of Patients with Hereditary Gastric Cancer “No Stomach for Cancer” for funding Seruca and Figueiredo research.
Databáze: OpenAIRE
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