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HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis

Perineural invasion (PNI) is a pathologic feature of pancreatic cancer and is associated with poor outcomes, metastasis, and recurrence in pancreatic cancer patients. However, the molecular mechanism of PNI remains unclear. The present study aimed to investigate the mechanism that HGF/c-Met pathway...

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Autores principales: Qin, Tao, Xiao, Ying, Qian, Weikun, Wang, Xueni, Gong, Mengyuan, Wang, Qiqi, An, Rui, Han, Liang, Duan, Wanxing, Ma, Qingyong, Wang, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023560/
https://www.ncbi.nlm.nih.gov/pubmed/35449152
http://dx.doi.org/10.1038/s41419-022-04799-5
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author Qin, Tao
Xiao, Ying
Qian, Weikun
Wang, Xueni
Gong, Mengyuan
Wang, Qiqi
An, Rui
Han, Liang
Duan, Wanxing
Ma, Qingyong
Wang, Zheng
author_facet Qin, Tao
Xiao, Ying
Qian, Weikun
Wang, Xueni
Gong, Mengyuan
Wang, Qiqi
An, Rui
Han, Liang
Duan, Wanxing
Ma, Qingyong
Wang, Zheng
author_sort Qin, Tao
collection PubMed
description Perineural invasion (PNI) is a pathologic feature of pancreatic cancer and is associated with poor outcomes, metastasis, and recurrence in pancreatic cancer patients. However, the molecular mechanism of PNI remains unclear. The present study aimed to investigate the mechanism that HGF/c-Met pathway facilitates the PNI of pancreatic cancer. In this study, we confirmed that c-Met expression was correlated with PNI in pancreatic cancer tissues. Activating the HGF/c-Met signaling pathway potentiated the expression of nerve growth factor (NGF) to recruit nerves and promote the PNI. Activating the HGF/c-Met signaling pathway also enhanced the migration and invasion ability of cancer cells to facilitate cancer cells invading nerves. Mechanistically, HGF/c-Met signaling pathway can active the mTOR/NGF axis to promote the PNI of pancreatic cancer. Additionally, we found that knocking down c-Met expression inhibited cancer cell migration along the nerve, reduced the damage of the sciatic nerve caused by cancer cells and protected the function of the sciatic nerve in vivo. Taken together, our findings suggest a supportive mechanism of the HGF/c-Met signaling pathway in promoting PNI by activating the mTOR/NGF axis in pancreatic cancer. Blocking the HGF/c-Met signaling pathway may be an effective target for the treatment of PNI.
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spelling pubmed-90235602022-04-28 HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis Qin, Tao Xiao, Ying Qian, Weikun Wang, Xueni Gong, Mengyuan Wang, Qiqi An, Rui Han, Liang Duan, Wanxing Ma, Qingyong Wang, Zheng Cell Death Dis Article Perineural invasion (PNI) is a pathologic feature of pancreatic cancer and is associated with poor outcomes, metastasis, and recurrence in pancreatic cancer patients. However, the molecular mechanism of PNI remains unclear. The present study aimed to investigate the mechanism that HGF/c-Met pathway facilitates the PNI of pancreatic cancer. In this study, we confirmed that c-Met expression was correlated with PNI in pancreatic cancer tissues. Activating the HGF/c-Met signaling pathway potentiated the expression of nerve growth factor (NGF) to recruit nerves and promote the PNI. Activating the HGF/c-Met signaling pathway also enhanced the migration and invasion ability of cancer cells to facilitate cancer cells invading nerves. Mechanistically, HGF/c-Met signaling pathway can active the mTOR/NGF axis to promote the PNI of pancreatic cancer. Additionally, we found that knocking down c-Met expression inhibited cancer cell migration along the nerve, reduced the damage of the sciatic nerve caused by cancer cells and protected the function of the sciatic nerve in vivo. Taken together, our findings suggest a supportive mechanism of the HGF/c-Met signaling pathway in promoting PNI by activating the mTOR/NGF axis in pancreatic cancer. Blocking the HGF/c-Met signaling pathway may be an effective target for the treatment of PNI. Nature Publishing Group UK 2022-04-21 /pmc/articles/PMC9023560/ /pubmed/35449152 http://dx.doi.org/10.1038/s41419-022-04799-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Qin, Tao
Xiao, Ying
Qian, Weikun
Wang, Xueni
Gong, Mengyuan
Wang, Qiqi
An, Rui
Han, Liang
Duan, Wanxing
Ma, Qingyong
Wang, Zheng
HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis
title HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis
title_full HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis
title_fullStr HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis
title_full_unstemmed HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis
title_short HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis
title_sort hgf/c-met pathway facilitates the perineural invasion of pancreatic cancer by activating the mtor/ngf axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023560/
https://www.ncbi.nlm.nih.gov/pubmed/35449152
http://dx.doi.org/10.1038/s41419-022-04799-5
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