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Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis
Neuropilin-1 (NRP1), a non–tyrosine kinase receptor, is overexpressed in many cancers including pancreatic and lung cancers. Inhibition of NRP1 expression, however, has differing pro-tumor vs. anti-tumor effects, depending on the cancer types. To understand the differential role of NRP1 in tumorigen...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635066/ https://www.ncbi.nlm.nih.gov/pubmed/29018205 http://dx.doi.org/10.1038/s41598-017-12992-2 |
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author | Vivekanandhan, Sneha Yang, Lijuan Cao, Ying Wang, Engfeng Dutta, Shamit K. Sharma, Anil K. Mukhopadhyay, Debabrata |
author_facet | Vivekanandhan, Sneha Yang, Lijuan Cao, Ying Wang, Engfeng Dutta, Shamit K. Sharma, Anil K. Mukhopadhyay, Debabrata |
author_sort | Vivekanandhan, Sneha |
collection | PubMed |
description | Neuropilin-1 (NRP1), a non–tyrosine kinase receptor, is overexpressed in many cancers including pancreatic and lung cancers. Inhibition of NRP1 expression, however, has differing pro-tumor vs. anti-tumor effects, depending on the cancer types. To understand the differential role of NRP1 in tumorigenesis process, we utilized cells from two different cancer types, pancreatic and lung, each containing either wild type KRAS (KRAS (wt)) or mutant KRAS (KRAS (mt)). Inhibition of NRP1 expression by shRNA in both pancreatic and lung cancer cells containing dominant active KRAS (mt) caused increased cell viability and tumor growth. On the contrary, inhibition of NRP1, in the tumor cells containing KRAS (wt) showed decreased tumor growth. Importantly, concurrent inhibition of KRAS (mt) and NRP1 in the tumor cells reverses the increased viability and leads to tumor inhibition. We found that NRP1 shRNA expressing KRAS (mt) tumor cells caused increased cell viability by decreasing SMAD2 phosphorylation. Our findings demonstrate that the effects of NRP1 knockdown in cancer cells are dependent on the genetic status of KRAS. |
format | Online Article Text |
id | pubmed-5635066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56350662017-10-18 Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis Vivekanandhan, Sneha Yang, Lijuan Cao, Ying Wang, Engfeng Dutta, Shamit K. Sharma, Anil K. Mukhopadhyay, Debabrata Sci Rep Article Neuropilin-1 (NRP1), a non–tyrosine kinase receptor, is overexpressed in many cancers including pancreatic and lung cancers. Inhibition of NRP1 expression, however, has differing pro-tumor vs. anti-tumor effects, depending on the cancer types. To understand the differential role of NRP1 in tumorigenesis process, we utilized cells from two different cancer types, pancreatic and lung, each containing either wild type KRAS (KRAS (wt)) or mutant KRAS (KRAS (mt)). Inhibition of NRP1 expression by shRNA in both pancreatic and lung cancer cells containing dominant active KRAS (mt) caused increased cell viability and tumor growth. On the contrary, inhibition of NRP1, in the tumor cells containing KRAS (wt) showed decreased tumor growth. Importantly, concurrent inhibition of KRAS (mt) and NRP1 in the tumor cells reverses the increased viability and leads to tumor inhibition. We found that NRP1 shRNA expressing KRAS (mt) tumor cells caused increased cell viability by decreasing SMAD2 phosphorylation. Our findings demonstrate that the effects of NRP1 knockdown in cancer cells are dependent on the genetic status of KRAS. Nature Publishing Group UK 2017-10-10 /pmc/articles/PMC5635066/ /pubmed/29018205 http://dx.doi.org/10.1038/s41598-017-12992-2 Text en © The Author(s) 2017 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/. |
spellingShingle | Article Vivekanandhan, Sneha Yang, Lijuan Cao, Ying Wang, Engfeng Dutta, Shamit K. Sharma, Anil K. Mukhopadhyay, Debabrata Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis |
title | Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis |
title_full | Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis |
title_fullStr | Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis |
title_full_unstemmed | Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis |
title_short | Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis |
title_sort | genetic status of kras modulates the role of neuropilin-1 in tumorigenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635066/ https://www.ncbi.nlm.nih.gov/pubmed/29018205 http://dx.doi.org/10.1038/s41598-017-12992-2 |
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