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Neuropilin-1 promotes the oncogenic Tenascin-C/integrin β3 pathway and modulates chemoresistance in breast cancer cells

Overview of attention for article published in BMC Cancer, May 2018
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Title
Neuropilin-1 promotes the oncogenic Tenascin-C/integrin β3 pathway and modulates chemoresistance in breast cancer cells
Published in
BMC Cancer, May 2018
DOI 10.1186/s12885-018-4446-y
Pubmed ID
Authors

Adviti Naik, Aida Al-Yahyaee, Nada Abdullah, Juda-El Sam, Noura Al-Zeheimi, Mahmoud W. Yaish, Sirin A. Adham

Abstract

Neuropilin-1 (NRP-1), a non-tyrosine kinase glycoprotein receptor, is associated with poor prognosis breast cancer, however transcriptomic changes triggered by NRP-1 overexpression and its association with chemoresistance in breast cancer have not yet been explored. BT-474 NRP-1 variant cells were generated by stable overexpression of NRP-1 in the BT-474 breast cancer cell line. RNA sequencing and qRT-PCR were conducted to identify differentially expressed genes. The role of an upregulated oncogene, Tenascin C (TNC) and its associated pathway was investigated by siRNA-mediated knockdown. Resistant variants of the control and BT-474 NRP-1 cells were generated by sequential treatment with four cycles of Adriamycin/Cyclophosphamide (4xAC) followed by four cycles of Paclitaxel (4xAC + 4xPAC). NRP-1 overexpression increased cellular tumorigenic behavior. RNA sequencing identified upregulation of an oncogene, Tenascin-C (TNC) and downregulation of several tumor suppressors in BT-474 NRP-1 cells. Additionally, protein analysis indicated activation of the TNC-associated integrin β3 (ITGB3) pathway via focal adhesion kinase (FAK), Akt (Ser473) and nuclear factor kappa B (NF-kB) p65. siRNA-mediated TNC knockdown ablated the migratory capacity of BT-474 NRP-1 cells and inactivated FAK/Akt473 signaling. NRP-1 overexpressing cells downregulated breast cancer resistance protein (BCRP/ABCG2). Consequently, sequential treatment with Adriamycin/Cyclophosphamide (AC) cytotoxic drugs to generate resistant cells indicated that BT-474 NRP-1 cells increased sensitivity to treatment by inactivating NRP-1/ITGB3/FAK/Akt/NF-kB p65 signaling compared to wild-type BT-474 resistant cells. We thus report a novel mechanism correlating high baseline NRP-1 with upregulated TNC/ITGB3 signaling, but decreased ABCG2 expression, which sensitizes BT-474 NRP-1 cells to Adriamycin/Cyclophosphamide. The study emphasizes on the targetability of the NRP-1/ITGB3 axis and its potential as a predictive biomarker for chemotherapy response.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 36 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 17%
Student > Master 5 14%
Student > Doctoral Student 5 14%
Student > Ph. D. Student 4 11%
Researcher 3 8%
Other 4 11%
Unknown 9 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 42%
Medicine and Dentistry 5 14%
Immunology and Microbiology 2 6%
Social Sciences 1 3%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Other 2 6%
Unknown 10 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 May 2018.
All research outputs
#11,493,024
of 12,931,128 outputs
Outputs from BMC Cancer
#3,932
of 4,809 outputs
Outputs of similar age
#234,127
of 270,100 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
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