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Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells

BACKGROUND: The 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in several tumourigenic-promoting processes including cellular viability maintenance and apoptotic evasion. Thus, the aim of this study was to assess the molecular mechanism of LRP/LR on apoptotic pathways in late stage (DLD-1) colo...

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Autores principales: Vania, Leila, Morris, Gavin, Ferreira, Eloise, Weiss, Stefan F. T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035741/
https://www.ncbi.nlm.nih.gov/pubmed/33836696
http://dx.doi.org/10.1186/s12885-021-08081-3
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author Vania, Leila
Morris, Gavin
Ferreira, Eloise
Weiss, Stefan F. T.
author_facet Vania, Leila
Morris, Gavin
Ferreira, Eloise
Weiss, Stefan F. T.
author_sort Vania, Leila
collection PubMed
description BACKGROUND: The 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in several tumourigenic-promoting processes including cellular viability maintenance and apoptotic evasion. Thus, the aim of this study was to assess the molecular mechanism of LRP/LR on apoptotic pathways in late stage (DLD-1) colorectal cancer cells upon siRNA-mediated down-regulation of LRP/LR. METHODS: siRNAs were used to down-regulate the expression of LRP/LR in DLD-1 cells which was assessed using western blotting and qPCR. To evaluate the mechanistic role of LRP/LR, proteomic analysis of pathways involved in proliferation and apoptosis were investigated. The data from the study was analysed using a one-way ANOVA, followed by a two-tailed student’s t-test with a confidence interval of 95%. RESULTS: Here we show that knock-down of LRP/LR led to significant changes in the proteome of DLD-1 cells, exposing new roles of the protein. Moreover, analysis showed that LRP/LR may alter components of the MAPK, p53-apoptotic and autophagic signalling pathways to aid colorectal cancer cells in continuous growth and survival. Knock-down of LRP/LR also resulted in significant decreases in telomerase activity and telomerase-related proteins in the DLD-1 cells. CONCLUSIONS: These findings show that LRP/LR is critically implicated in apoptosis and cell viability maintenance and suggest that siRNA-mediated knock-down of LRP/LR may be a possible therapeutic strategy for the treatment of colorectal cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08081-3.
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spelling pubmed-80357412021-04-12 Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells Vania, Leila Morris, Gavin Ferreira, Eloise Weiss, Stefan F. T. BMC Cancer Research Article BACKGROUND: The 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in several tumourigenic-promoting processes including cellular viability maintenance and apoptotic evasion. Thus, the aim of this study was to assess the molecular mechanism of LRP/LR on apoptotic pathways in late stage (DLD-1) colorectal cancer cells upon siRNA-mediated down-regulation of LRP/LR. METHODS: siRNAs were used to down-regulate the expression of LRP/LR in DLD-1 cells which was assessed using western blotting and qPCR. To evaluate the mechanistic role of LRP/LR, proteomic analysis of pathways involved in proliferation and apoptosis were investigated. The data from the study was analysed using a one-way ANOVA, followed by a two-tailed student’s t-test with a confidence interval of 95%. RESULTS: Here we show that knock-down of LRP/LR led to significant changes in the proteome of DLD-1 cells, exposing new roles of the protein. Moreover, analysis showed that LRP/LR may alter components of the MAPK, p53-apoptotic and autophagic signalling pathways to aid colorectal cancer cells in continuous growth and survival. Knock-down of LRP/LR also resulted in significant decreases in telomerase activity and telomerase-related proteins in the DLD-1 cells. CONCLUSIONS: These findings show that LRP/LR is critically implicated in apoptosis and cell viability maintenance and suggest that siRNA-mediated knock-down of LRP/LR may be a possible therapeutic strategy for the treatment of colorectal cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08081-3. BioMed Central 2021-04-09 /pmc/articles/PMC8035741/ /pubmed/33836696 http://dx.doi.org/10.1186/s12885-021-08081-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Vania, Leila
Morris, Gavin
Ferreira, Eloise
Weiss, Stefan F. T.
Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells
title Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells
title_full Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells
title_fullStr Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells
title_full_unstemmed Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells
title_short Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells
title_sort knock-down of lrp/lr influences signalling pathways in late-stage colorectal carcinoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035741/
https://www.ncbi.nlm.nih.gov/pubmed/33836696
http://dx.doi.org/10.1186/s12885-021-08081-3
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