The University of Southampton
University of Southampton Institutional Repository

Unregulated smooth-muscle myosin in human intestinal neoplasia

Unregulated smooth-muscle myosin in human intestinal neoplasia
Unregulated smooth-muscle myosin in human intestinal neoplasia
A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz-jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP. We found somatic protein-elongating frameshift mutations in 55% of CRCs displaying microsatellite instability and in the germ-line of one individual with PJS. Additionally, two somatic missense mutations were found in one microsatellite stable CRC. These two missense mutations, R501L and K1044N, and the frameshift mutations were functionally evaluated. All mutations resulted in unregulated molecules displaying constitutive motor activity, similar to the mutant myosin underlying mlt. Thus, MYH11 mutations appear to contribute also to human intestinal neoplasia. Unregulated MYH11 may affect the cellular energy balance or disturb cell lineage decisions in tumor progenitor cells. These data challenge our view on MYH11 as a passive differentiation marker functioning in muscle contraction and add to our understanding of intestinal neoplasia
colorectal cancer, microsatellite instability, peutz–Jeghers syndrome, smmhc/myh11
0027-8424
5513-5518
Alhopuro, Pia
1fe22ee6-a055-4c94-b55f-dffd09815d02
Phichith, Denis
6f676c6a-078d-4d9f-8413-52095642f3aa
Tuupanen, Sari
f2522a59-f70b-4d0f-94d5-ba1c69b4d587
Sammalkorpi, Heli
55769cfd-dba1-4d5d-ab83-302a99de129b
Nybondas, Miranda
34a068b4-e62d-47b2-bc12-98236df858da
Saharinen, Juha
27c11155-e84a-41df-8b29-93c03ba25710
Robinson, James P.
69debbe2-4fd3-46dd-b69d-0f74008e76ca
Yang, Zhaohui
a3900148-3bb1-4bbc-be9e-b852f6dd8c44
Chen, Li-Qiong
6c9b8388-d16c-4e98-9049-3f09fb4e2cfb
Orntoft, Torben
efbcadb2-18b9-448d-82c4-ff2e3c74b575
Mecklin, Jukka-Pekka
5e4b3d86-d108-401b-9199-39e97c1c333e
Järvinen, Heikki
61706e11-240a-43fd-86e1-ea81a42ed6ac
Eng, Charis
249f0609-040a-47de-8c3c-c77d9823a230
Moeslein, Gabriela
cd90e701-7373-43d6-8ff4-f7e14e4f6425
Shibata, Darryl
20f13bda-6642-46b7-8760-473b04334c3f
Houlston, Richard S.
0292e06f-2fd2-4b71-a629-00b288016474
Lucassen, Anneke
2eb85efc-c6e8-4c3f-b963-0290f6c038a5
Tomlinson, Ian P.M.
0142a37c-4819-4473-a9a7-90f617b5355e
Launonen, Virpi
89a2a598-4725-411f-b411-92723ae16053
Ristimäk, Ari
3501fe86-d515-40be-ba93-5f04f970dba7
Arango, Diego
f2faefe4-a180-4fc1-8a91-ef36aa3b21a2
Karhu, Auli
b0ebd43a-6a3b-477c-97e2-39bdca785073
Sweeney, H. Lee
aa0d0f30-7846-4edd-8ae1-15293c72df7e
Aaltonen, Lauri A.
1f26d3d5-721c-4652-8a77-95debd33275a
Alhopuro, Pia
1fe22ee6-a055-4c94-b55f-dffd09815d02
Phichith, Denis
6f676c6a-078d-4d9f-8413-52095642f3aa
Tuupanen, Sari
f2522a59-f70b-4d0f-94d5-ba1c69b4d587
Sammalkorpi, Heli
55769cfd-dba1-4d5d-ab83-302a99de129b
Nybondas, Miranda
34a068b4-e62d-47b2-bc12-98236df858da
Saharinen, Juha
27c11155-e84a-41df-8b29-93c03ba25710
Robinson, James P.
69debbe2-4fd3-46dd-b69d-0f74008e76ca
Yang, Zhaohui
a3900148-3bb1-4bbc-be9e-b852f6dd8c44
Chen, Li-Qiong
6c9b8388-d16c-4e98-9049-3f09fb4e2cfb
Orntoft, Torben
efbcadb2-18b9-448d-82c4-ff2e3c74b575
Mecklin, Jukka-Pekka
5e4b3d86-d108-401b-9199-39e97c1c333e
Järvinen, Heikki
61706e11-240a-43fd-86e1-ea81a42ed6ac
Eng, Charis
249f0609-040a-47de-8c3c-c77d9823a230
Moeslein, Gabriela
cd90e701-7373-43d6-8ff4-f7e14e4f6425
Shibata, Darryl
20f13bda-6642-46b7-8760-473b04334c3f
Houlston, Richard S.
0292e06f-2fd2-4b71-a629-00b288016474
Lucassen, Anneke
2eb85efc-c6e8-4c3f-b963-0290f6c038a5
Tomlinson, Ian P.M.
0142a37c-4819-4473-a9a7-90f617b5355e
Launonen, Virpi
89a2a598-4725-411f-b411-92723ae16053
Ristimäk, Ari
3501fe86-d515-40be-ba93-5f04f970dba7
Arango, Diego
f2faefe4-a180-4fc1-8a91-ef36aa3b21a2
Karhu, Auli
b0ebd43a-6a3b-477c-97e2-39bdca785073
Sweeney, H. Lee
aa0d0f30-7846-4edd-8ae1-15293c72df7e
Aaltonen, Lauri A.
1f26d3d5-721c-4652-8a77-95debd33275a

Alhopuro, Pia, Phichith, Denis, Tuupanen, Sari, Sammalkorpi, Heli, Nybondas, Miranda, Saharinen, Juha, Robinson, James P., Yang, Zhaohui, Chen, Li-Qiong, Orntoft, Torben, Mecklin, Jukka-Pekka, Järvinen, Heikki, Eng, Charis, Moeslein, Gabriela, Shibata, Darryl, Houlston, Richard S., Lucassen, Anneke, Tomlinson, Ian P.M., Launonen, Virpi, Ristimäk, Ari, Arango, Diego, Karhu, Auli, Sweeney, H. Lee and Aaltonen, Lauri A. (2008) Unregulated smooth-muscle myosin in human intestinal neoplasia. Proceedings of the National Academy of Sciences, 105 (14), 5513-5518. (doi:10.1073/pnas.0801213105).

Record type: Article

Abstract

A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz-jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP. We found somatic protein-elongating frameshift mutations in 55% of CRCs displaying microsatellite instability and in the germ-line of one individual with PJS. Additionally, two somatic missense mutations were found in one microsatellite stable CRC. These two missense mutations, R501L and K1044N, and the frameshift mutations were functionally evaluated. All mutations resulted in unregulated molecules displaying constitutive motor activity, similar to the mutant myosin underlying mlt. Thus, MYH11 mutations appear to contribute also to human intestinal neoplasia. Unregulated MYH11 may affect the cellular energy balance or disturb cell lineage decisions in tumor progenitor cells. These data challenge our view on MYH11 as a passive differentiation marker functioning in muscle contraction and add to our understanding of intestinal neoplasia

Full text not available from this repository.

More information

Published date: 7 April 2008
Keywords: colorectal cancer, microsatellite instability, peutz–Jeghers syndrome, smmhc/myh11
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 62668
URI: https://eprints.soton.ac.uk/id/eprint/62668
ISSN: 0027-8424
PURE UUID: b59774c4-6f8b-4d1e-8f2a-22e6dfaf503c

Catalogue record

Date deposited: 07 Oct 2008
Last modified: 13 Mar 2019 20:27

Export record

Altmetrics

Contributors

Author: Pia Alhopuro
Author: Denis Phichith
Author: Sari Tuupanen
Author: Heli Sammalkorpi
Author: Miranda Nybondas
Author: Juha Saharinen
Author: James P. Robinson
Author: Zhaohui Yang
Author: Li-Qiong Chen
Author: Torben Orntoft
Author: Jukka-Pekka Mecklin
Author: Heikki Järvinen
Author: Charis Eng
Author: Gabriela Moeslein
Author: Darryl Shibata
Author: Richard S. Houlston
Author: Anneke Lucassen
Author: Ian P.M. Tomlinson
Author: Virpi Launonen
Author: Ari Ristimäk
Author: Diego Arango
Author: Auli Karhu
Author: H. Lee Sweeney
Author: Lauri A. Aaltonen

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×