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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MDPI AG
2022-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/2/280 |
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| author | Laura Bizzozero Margherita Pergolizzi Davide Pascal Elena Maldi Giulia Villari Jessica Erriquez Marco Volante Guido Serini Caterina Marchiò Federico Bussolino Marco Arese |
| author_facet | Laura Bizzozero Margherita Pergolizzi Davide Pascal Elena Maldi Giulia Villari Jessica Erriquez Marco Volante Guido Serini Caterina Marchiò Federico Bussolino Marco Arese |
| author_sort | Laura Bizzozero |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T01:44:27Z |
| format | Article |
| id | doaj.art-a33d18ec17d548f581c5920beba0a114 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:44:27Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a33d18ec17d548f581c5920beba0a1142023-11-23T13:18:58ZengMDPI AGCells2073-44092022-01-0111228010.3390/cells11020280Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic FactorLaura Bizzozero0Margherita Pergolizzi1Davide Pascal2Elena Maldi3Giulia Villari4Jessica Erriquez5Marco Volante6Guido Serini7Caterina Marchiò8Federico Bussolino9Marco Arese10Department of Oncology, University of Torino, 10060 Candiolo, ItalyDepartment of Oncology, University of Torino, 10060 Candiolo, ItalyDepartment of Oncology, University of Torino, 10060 Candiolo, ItalyPathology Unit, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyDepartment of Oncology, University of Torino, 10060 Candiolo, ItalyCandiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyDepartment of Oncology, University of Torino, 10060 Candiolo, ItalyDepartment of Oncology, University of Torino, 10060 Candiolo, ItalyPathology Unit, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, ItalyDepartment of Oncology, University of Torino, 10060 Candiolo, ItalyDepartment of Oncology, University of Torino, 10060 Candiolo, ItalyMany 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.https://www.mdpi.com/2073-4409/11/2/280tumor–nervous connectionsneuroligin 1glial cell line-derived neurotrophic factorcofilinfilopodia |
| spellingShingle | Laura Bizzozero Margherita Pergolizzi Davide Pascal Elena Maldi Giulia Villari Jessica Erriquez Marco Volante Guido Serini Caterina Marchiò Federico Bussolino Marco Arese Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor Cells tumor–nervous connections neuroligin 1 glial cell line-derived neurotrophic factor cofilin filopodia |
| 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 | tumor–nervous connections neuroligin 1 glial cell line-derived neurotrophic factor cofilin filopodia |
| url | https://www.mdpi.com/2073-4409/11/2/280 |
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