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Tumoral Neuroligin 1 Promotes Cancer-Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor.
Bizzozero, Laura; Pergolizzi, Margherita; Pascal, Davide; Maldi, Elena; Villari, Giulia; Erriquez, Jessica; Volante, Marco; Serini, Guido; Marchiò, Caterina; Bussolino, Federico; Arese, Marco.
Afiliação
  • Bizzozero L; Department of Oncology, University of Torino, 10060 Candiolo, Italy.
  • Pergolizzi M; Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
  • Pascal D; Department of Oncology, University of Torino, 10060 Candiolo, Italy.
  • Maldi E; Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
  • Villari G; Department of Oncology, University of Torino, 10060 Candiolo, Italy.
  • Erriquez J; Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
  • Volante M; Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
  • Serini G; Department of Oncology, University of Torino, 10060 Candiolo, Italy.
  • Marchiò C; Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
  • Bussolino F; Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
  • Arese M; Department of Oncology, University of Torino, 10060 Candiolo, Italy.
Cells ; 11(2)2022 01 14.
Article em En | MEDLINE | ID: mdl-35053395
Many nervous proteins are expressed in cancer cells. In this report, we asked whether the synaptic protein neuroligin 1 (NLGN1) was expressed by prostatic and pancreatic carcinomas; in addition, given the tendency of these tumors to interact with nerves, we asked whether NLGN1 played a role in this process. Through immunohistochemistry on human tissue microarrays, we showed that NLGN1 is expressed by prostatic and pancreatic cancer tissues in discrete stages and tumor districts. Next, we performed in vitro and in vivo assays, demonstrating that NLGN1 promotes cancer cell invasion and migration along nerves. Because of the established role of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) in tumor-nerve interactions, we assessed a potential NLGN1-GDNF cooperation. We found that blocking GDNF activity with a specific antibody completely inhibited NLGN1-induced in vitro cancer cell invasion of nerves. Finally, we demonstrated that, in the presence of NLGN1, GDNF markedly activates cofilin, a cytoskeletal regulatory protein, altering filopodia dynamics. In conclusion, our data further prove the existence of a molecular and functional cross-talk between the nervous system and cancer cells. NLGN1 was shown here to function along one of the most represented neurotrophic factors in the nerve microenvironment, possibly opening new therapeutic avenues.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Moléculas de Adesão Celular Neuronais / Fator Neurotrófico Derivado de Linhagem de Célula Glial / Neoplasias / Tecido Nervoso Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Moléculas de Adesão Celular Neuronais / Fator Neurotrófico Derivado de Linhagem de Célula Glial / Neoplasias / Tecido Nervoso Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article