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Sunderland Repository records the research produced by the University of Sunderland including practice-based research and theses.

Ran GTPase promotes cancer progression via Met receptormediated downstream signaling

Yuen, Hiu-Fung, Chan, Ka-Kui, Platt-Higgins, Angela, Dakir, EL-Habib, Matchett, Kyle B., Ahmed Haggag, Yusuf, Jithesh, Puthen V., Habib, Tanwir, Faheem, Ahmed, Dean, Fennell A., Morgan, Richard, Rudland, Philip S. and El-Tanani, Mohamed (2016) Ran GTPase promotes cancer progression via Met receptormediated downstream signaling. Oncotarget, 7. pp. 75854-75864. ISSN 1949-2553

Item Type: Article


It has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival.
Here, we show that knockdown of Ran leads to a reduction of Met receptor expression in several breast and lung cancer cell lines. This, in turn suppressed HGF expression and the Met-mediated activation of the Akt pathway, as well as cell adhesion, migration, and invasion. In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. We further demonstrate that Met reduction-mediated by knockdown of Ran, occurs at the post-transcriptional level, probably via a matrix metalloproteinase. Moreover, the level of immunoreactive Ran and Met are positively associated in human breast cancer specimens, suggesting that a high level of Ran may be a pre-requisite for Met overexpression. Interestingly, a high level of immunoreactive Ran dictates the prognostic significance of Met, indicating that the co-overexpression of Met and Ran may be associated with cancer progression and could be used in combination as a prognostic indicator.

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Depositing User: Barry Hall


Item ID: 6780
Identification Number:
ISSN: 1949-2553
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Date Deposited: 02 Nov 2016 09:54
Last Modified: 30 Sep 2020 11:17


Author: Hiu-Fung Yuen
Author: Ka-Kui Chan
Author: Angela Platt-Higgins
Author: EL-Habib Dakir
Author: Kyle B. Matchett
Author: Yusuf Ahmed Haggag
Author: Puthen V. Jithesh
Author: Tanwir Habib
Author: Ahmed Faheem
Author: Fennell A. Dean
Author: Richard Morgan
Author: Philip S. Rudland
Author: Mohamed El-Tanani

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences


Sciences > Pharmacy and Pharmacology

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