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Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor

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...

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Autores principales: Bizzozero, Laura, Pergolizzi, Margherita, Pascal, Davide, Maldi, Elena, Villari, Giulia, Erriquez, Jessica, Volante, Marco, Serini, Guido, Marchiò, Caterina, Bussolino, Federico, Arese, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774081/
https://www.ncbi.nlm.nih.gov/pubmed/35053395
http://dx.doi.org/10.3390/cells11020280
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author Bizzozero, Laura
Pergolizzi, Margherita
Pascal, Davide
Maldi, Elena
Villari, Giulia
Erriquez, Jessica
Volante, Marco
Serini, Guido
Marchiò, Caterina
Bussolino, Federico
Arese, Marco
author_facet Bizzozero, Laura
Pergolizzi, Margherita
Pascal, Davide
Maldi, Elena
Villari, Giulia
Erriquez, Jessica
Volante, Marco
Serini, Guido
Marchiò, Caterina
Bussolino, Federico
Arese, Marco
author_sort Bizzozero, Laura
collection PubMed
description 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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spelling pubmed-87740812022-01-21 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 Cells Article 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. MDPI 2022-01-14 /pmc/articles/PMC8774081/ /pubmed/35053395 http://dx.doi.org/10.3390/cells11020280 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bizzozero, Laura
Pergolizzi, Margherita
Pascal, Davide
Maldi, Elena
Villari, Giulia
Erriquez, Jessica
Volante, Marco
Serini, Guido
Marchiò, Caterina
Bussolino, Federico
Arese, Marco
Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor
title Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor
title_full Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor
title_fullStr Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor
title_full_unstemmed Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor
title_short Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor
title_sort tumoral neuroligin 1 promotes cancer–nerve interactions and synergizes with the glial cell line-derived neurotrophic factor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774081/
https://www.ncbi.nlm.nih.gov/pubmed/35053395
http://dx.doi.org/10.3390/cells11020280
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