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

Sneha Vivekanandhan, Lijuan Yang, Ying Cao, Engfeng Wang, Shamit K. Dutta, Anil K. Sharma, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number12877
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Neuropilin-1
Carcinogenesis
Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Small Interfering RNA
Cell Survival
Growth

ASJC Scopus subject areas

  • General

Cite this

Vivekanandhan, S., Yang, L., Cao, Y., Wang, E., Dutta, S. K., Sharma, A. K., & Mukhopadhyay, D. (2017). Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis. Scientific Reports, 7(1), [12877]. https://doi.org/10.1038/s41598-017-12992-2

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.

In: Scientific Reports, Vol. 7, No. 1, 12877, 01.12.2017.

Research output: Contribution to journalArticle

Vivekanandhan S, Yang L, Cao Y, Wang E, Dutta SK, Sharma AK et al. Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis. Scientific Reports. 2017 Dec 1;7(1). 12877. https://doi.org/10.1038/s41598-017-12992-2
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. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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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.",
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