Lamin A/C is a risk biomarker in colorectal cancer.

<h4>Background</h4>A-type lamins are type V intermediate filament proteins encoded by the gene LMNA. Mutations in LMNA give rise to diverse degenerative diseases related to premature ageing. A-type lamins also influence the activity of the Retinoblastoma protein (pRb) and oncogenes such...

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Autores principales:	Naomi D Willis, Thomas R Cox, Syed F Rahman-Casañs, Kim Smits, Stefan A Przyborski, Piet van den Brandt, Manon van Engeland, Matty Weijenberg, Robert G Wilson, Adriaan de Bruïne, Christopher J Hutchison
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db3d2cfb44af49da8812d1846bf6a64c
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spelling	oai:doaj.org-article:db3d2cfb44af49da8812d1846bf6a64c2021-11-25T06:11:10ZLamin A/C is a risk biomarker in colorectal cancer.1932-620310.1371/journal.pone.0002988https://doaj.org/article/db3d2cfb44af49da8812d1846bf6a64c2008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18714339/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>A-type lamins are type V intermediate filament proteins encoded by the gene LMNA. Mutations in LMNA give rise to diverse degenerative diseases related to premature ageing. A-type lamins also influence the activity of the Retinoblastoma protein (pRb) and oncogenes such a beta-catenin. Consequently, it has been speculated that expression of A-type lamins may also influence tumour progression.<h4>Methodology/principal findings</h4>An archive of colorectal cancer (CRC) and normal colon tissue was screened for expression of A-type lamins. We used the Cox proportional hazard ratio (HR) method to investigate patient survival. Using CRC cell lines we investigated the effects of lamin A expression on other genes by RT-PCR; on cell growth by FACS analysis; and on invasiveness by cell migration assays and siRNA knockdown of targeted genes. We found that lamin A is expressed in colonic stem cells and that patients with A-type lamin-expressing tumours have significantly worse prognosis than patients with A-type lamin negative tumours (HR = 1.85, p = 0.005). To understand this finding, we established a model system based upon expression of GFP-lamin A in CRC cells. We found that expression of GFP-lamin A in these cells did not affect cell proliferation but did promote greatly increased cell motility and invasiveness. The reason for this increased invasiveness was that expression of lamin A promoted up-regulation of the actin bundling protein T-plastin, leading to down regulation of the cell adhesion molecule E-cadherin.<h4>Conclusions</h4>Expression of A-type lamins increases the risk of death from CRC because its presence gives rise to increased invasiveness and potentially a more stem cell-like phenotype. This report directly links A-type lamin expression to tumour progression and raises the profile of LMNA from one implicated in multiple but rare genetic conditions to a gene involved in one of the commonest diseases in the Western World.Naomi D WillisThomas R CoxSyed F Rahman-CasañsKim SmitsStefan A PrzyborskiPiet van den BrandtManon van EngelandMatty WeijenbergRobert G WilsonAdriaan de BruïneChristopher J HutchisonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e2988 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naomi D Willis Thomas R Cox Syed F Rahman-Casañs Kim Smits Stefan A Przyborski Piet van den Brandt Manon van Engeland Matty Weijenberg Robert G Wilson Adriaan de Bruïne Christopher J Hutchison Lamin A/C is a risk biomarker in colorectal cancer.
description	<h4>Background</h4>A-type lamins are type V intermediate filament proteins encoded by the gene LMNA. Mutations in LMNA give rise to diverse degenerative diseases related to premature ageing. A-type lamins also influence the activity of the Retinoblastoma protein (pRb) and oncogenes such a beta-catenin. Consequently, it has been speculated that expression of A-type lamins may also influence tumour progression.<h4>Methodology/principal findings</h4>An archive of colorectal cancer (CRC) and normal colon tissue was screened for expression of A-type lamins. We used the Cox proportional hazard ratio (HR) method to investigate patient survival. Using CRC cell lines we investigated the effects of lamin A expression on other genes by RT-PCR; on cell growth by FACS analysis; and on invasiveness by cell migration assays and siRNA knockdown of targeted genes. We found that lamin A is expressed in colonic stem cells and that patients with A-type lamin-expressing tumours have significantly worse prognosis than patients with A-type lamin negative tumours (HR = 1.85, p = 0.005). To understand this finding, we established a model system based upon expression of GFP-lamin A in CRC cells. We found that expression of GFP-lamin A in these cells did not affect cell proliferation but did promote greatly increased cell motility and invasiveness. The reason for this increased invasiveness was that expression of lamin A promoted up-regulation of the actin bundling protein T-plastin, leading to down regulation of the cell adhesion molecule E-cadherin.<h4>Conclusions</h4>Expression of A-type lamins increases the risk of death from CRC because its presence gives rise to increased invasiveness and potentially a more stem cell-like phenotype. This report directly links A-type lamin expression to tumour progression and raises the profile of LMNA from one implicated in multiple but rare genetic conditions to a gene involved in one of the commonest diseases in the Western World.
format	article
author	Naomi D Willis Thomas R Cox Syed F Rahman-Casañs Kim Smits Stefan A Przyborski Piet van den Brandt Manon van Engeland Matty Weijenberg Robert G Wilson Adriaan de Bruïne Christopher J Hutchison
author_facet	Naomi D Willis Thomas R Cox Syed F Rahman-Casañs Kim Smits Stefan A Przyborski Piet van den Brandt Manon van Engeland Matty Weijenberg Robert G Wilson Adriaan de Bruïne Christopher J Hutchison
author_sort	Naomi D Willis
title	Lamin A/C is a risk biomarker in colorectal cancer.
title_short	Lamin A/C is a risk biomarker in colorectal cancer.
title_full	Lamin A/C is a risk biomarker in colorectal cancer.
title_fullStr	Lamin A/C is a risk biomarker in colorectal cancer.
title_full_unstemmed	Lamin A/C is a risk biomarker in colorectal cancer.
title_sort	lamin a/c is a risk biomarker in colorectal cancer.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/db3d2cfb44af49da8812d1846bf6a64c
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Lamin A/C is a risk biomarker in colorectal cancer.

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