Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sneha Vivekanandhan, Lijuan Yang, Ying Cao, Engfeng Wang, Shamit K. Dutta, Anil K. Sharma, Debabrata Mukhopadhyay
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ee25eeec42b64df0ac2ab2c256fdf135
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ee25eeec42b64df0ac2ab2c256fdf135
record_format	dspace
spelling	oai:doaj.org-article:ee25eeec42b64df0ac2ab2c256fdf1352021-12-02T15:04:57ZGenetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis10.1038/s41598-017-12992-22045-2322https://doaj.org/article/ee25eeec42b64df0ac2ab2c256fdf1352017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-12992-2https://doaj.org/toc/2045-2322Abstract 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.Sneha VivekanandhanLijuan YangYing CaoEngfeng WangShamit K. DuttaAnil K. SharmaDebabrata MukhopadhyayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sneha Vivekanandhan Lijuan Yang Ying Cao Engfeng Wang Shamit K. Dutta Anil K. Sharma Debabrata Mukhopadhyay Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis
description	Abstract 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	article
author	Sneha Vivekanandhan Lijuan Yang Ying Cao Engfeng Wang Shamit K. Dutta Anil K. Sharma Debabrata Mukhopadhyay
author_facet	Sneha Vivekanandhan Lijuan Yang Ying Cao Engfeng Wang Shamit K. Dutta Anil K. Sharma Debabrata Mukhopadhyay
author_sort	Sneha Vivekanandhan
title	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_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_sort	genetic status of kras modulates the role of neuropilin-1 in tumorigenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ee25eeec42b64df0ac2ab2c256fdf135
work_keys_str_mv	AT snehavivekanandhan geneticstatusofkrasmodulatestheroleofneuropilin1intumorigenesis AT lijuanyang geneticstatusofkrasmodulatestheroleofneuropilin1intumorigenesis AT yingcao geneticstatusofkrasmodulatestheroleofneuropilin1intumorigenesis AT engfengwang geneticstatusofkrasmodulatestheroleofneuropilin1intumorigenesis AT shamitkdutta geneticstatusofkrasmodulatestheroleofneuropilin1intumorigenesis AT anilksharma geneticstatusofkrasmodulatestheroleofneuropilin1intumorigenesis AT debabratamukhopadhyay geneticstatusofkrasmodulatestheroleofneuropilin1intumorigenesis
_version_	1718388991215009792

Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis

Ejemplares similares