In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

Related resources

Full-text held externally

University researcher(s)

Academic department(s)

HUWE1 Ubiquitylates and Degrades the RAC Activator TIAM1 Promoting Cell-Cell Adhesion Disassembly, Migration, and Invasion.

Vaughan, Lynsey; Tan, Chong-Teik; Chapman, Anna; Nonaka, Daisuke; Mack, Natalie A; Smith, Duncan; Booton, Richard; Hurlstone, Adam F L; Malliri, Angeliki

Cell reports. 2015;10(1):88-102.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:

Full-text held externally

Abstract

The E3 ubiquitin ligase HUWE1, deregulated in carcinoma, has been implicated in tumor formation. Here, we uncover a role for HUWE1 in cell migration and invasion through degrading the RAC activator TIAM1, implying an additional function in malignant progression. In MDCKII cells in response to HGF, HUWE1 catalyzes TIAM1 ubiquitylation and degradation predominantly at cell-cell adhesions, facilitating junction disassembly, migration, and invasion. Depleting HUWE1 or mutating the TIAM1 ubiquitylation site prevents TIAM1 degradation, antagonizing scattering, and invasion. Moreover, simultaneous depletion of TIAM1 restores migration and invasion in HUWE1-depleted cells. Significantly, we show that HUWE1 stimulates human lung cancer cell invasion through regulating TIAM1 stability. Finally, we demonstrate that HUWE1 and TIAM1 protein levels are inversely correlated in human lung carcinomas. Thus, we elucidate a critical role for HUWE1 in regulating epithelial cell-cell adhesion and provide additional evidence that ubiquitylation contributes to spatiotemporal control of RAC.

Bibliographic metadata

Type of resource:
Content type:
Publication type:
Published date:
Journal title:
Abbreviated journal title:
ISSN:
Place of publication:
United States
Volume:
10
Issue:
1
Pagination:
88-102
Digital Object Identifier:
10.1016/j.celrep.2014.12.012
Pubmed Identifier:
25543140
Pii Identifier:
S2211-1247(14)01041-9
Access state:
Active

Institutional metadata

University researcher(s):
Academic department(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:247499
Created by:
Hurlstone, Adam
Created:
20th January, 2015, 10:25:46
Last modified by:
Hurlstone, Adam
Last modified:
11th December, 2015, 08:13:17

Can we help?

The library chat service will be available from 11am-3pm Monday to Friday (excluding Bank Holidays). You can also email your enquiry to us.