S100P is a molecular determinant of E-cadherin function in gastric cancer

Autor: Carla Oliveira, Maria Sofia Fernandes, Ana Margarida Moreira, Sérgia Velho, Raquel Almeida, Fernando Schmitt, Rita Barros, Joana Paredes, Raquel Seruca, Patrícia Carneiro, Patrícia Oliveira, Anabela Ferro, Joana Figueiredo, Fátima Carneiro
Přispěvatelé: Instituto de Investigação e Inovação em Saúde
Rok vydání: 2019
Předmět:
0301 basic medicine
Candidate gene
Survival
Regulator
lcsh:Medicine
Biochemistry
law.invention
Neoplasm Proteins / genetics
0302 clinical medicine
Cadherins / genetics
law
Stomach Neoplasms / metabolism
Tumor Cells
Cultured
Tissue microarray
lcsh:Cytology
Cadherins
Prognosis
Neoplasm Proteins
3. Good health
030220 oncology & carcinogenesis
Cadherins / metabolism
Signal Transduction
Context (language use)
03 medical and health sciences
Stomach Neoplasms
medicine
Humans
lcsh:QH573-671
Molecular Biology
Calcium-Binding Proteins / genetics
Cadherin
business.industry
Research
Calcium-Binding Proteins
lcsh:R
Calcium-Binding Proteins / metabolism
E-cadherin
Cancer
Cell Biology
Signal Transduction / genetics
medicine.disease
030104 developmental biology
Cancer cell
Cancer research
Suppressor
Stomach Neoplasms / pathology
Gastric cancer
business
Neoplasm Proteins / metabolism
S100P
Zdroj: Cell Communication and Signaling, Vol 17, Iss 1, Pp 1-13 (2019)
Cell Communication and Signaling : CCS
ISSN: 1478-811X
Popis: Background: E-cadherin has been awarded a key role in the aetiology of both sporadic and hereditary forms of gastric cancer. In this study, we aimed to identify molecular interactors that influence the expression and function of E-cadherin associated to cancer. Methods: A data mining approach was used to predict stomach-specific candidate genes, uncovering S100P as a key candidate. The role of S100P was evaluated through in vitro functional assays and its expression was studied in a gastric cancer tissue microarray (TMA). Results: S100P was found to contribute to a cancer pathway dependent on the context of E-cadherin function. In particular, we demonstrated that S100P acts as an E-cadherin positive regulator in a wild-type E-cadherin context, and its inhibition results in decreased E-cadherin expression and function. In contrast, S100P is likely to be a pro-survival factor in gastric cancer cells with loss of functional E-cadherin, contributing to an oncogenic molecular program. Moreover, expression analysis in a gastric cancer TMA revealed that S100P expression impacts negatively among patients bearing Ecad- tumours, despite not being significantly associated with overall survival on its own. Conclusions: We propose that S100P has a dual role in gastric cancer, acting as an oncogenic factor in the context of E-cadherin loss and as a tumour suppressor in a functional E-cadherin setting. The discovery of antagonist effects of S100P in different E-cadherin contexts will aid in the stratification of gastric cancer patients who may benefit from S100P-targeted therapies. This work was financed by FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE 2020), Programa Operacional de Competitividade e Internacionalização (POCI), Programa Operacional Regional do Norte (Norte 2020) and by National Funds through the Portuguese Foundation for Science and Technology (FCT), under the projects PTDC/BIMONC/0171/2012, PTDC/BIM-ONC/0281/2014, NORTE-01-0145-FEDER-000029, PTDC/MED-GEN/30356/2017, PTDC/BTM-SAL/30383/2017; doctoral grant SFRH/BD/114687/2016-AMM; post-doctoral grant SFRH/BPD/87705/2012-JF. We acknowledge the IFCT Program for funding JP and SV.
Databáze: OpenAIRE
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