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The critical role of dysregulated RhoB signaling pathway in radioresistance of colorectal cancer

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Title: The critical role of dysregulated RhoB signaling pathway in radioresistance of colorectal cancer
Authors: Liu, N
Cui, W
Jiang, X
Zhang, Z
Gnosa, S
Ali, Z
Jensen, L
Jönsson, J-I
Blockhuys, S
Lam, EW-F
Zhao, Z
Ping, J
Xie, N
Kopsida, M
Wang, X
Sun, X-F
Item Type: Journal Article
Abstract: Purpose To explore whether Rho protein was involved in the radioresistance of colorectal cancer and investigated the underlying mechanism. Methods and Materials Rho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established by CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was for detecting RhoB downstream signaling factors. RhoB and FOXM1 expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiotherapy trial. Results RhoB expression was related to radiation resistance. Complete depletion of RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish model. Probing signaling using mass cytometry-based single-cell analysis showed that Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells and the inhibition of FOXM1 led to lower survival rates, and attenuated migration and invasion abilities of the cells after radiation. In the patients with radiotherapy, RhoB overexpression was related to high FOXM1, late TNM stage, high distant recurrence and poor survival independent of other clinical factors. Conclusions RhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathway.
Issue Date: 27-Apr-2019
Date of Acceptance: 22-Apr-2019
URI: http://hdl.handle.net/10044/1/70269
DOI: https://dx.doi.org/10.1016/j.ijrobp.2019.04.021
ISSN: 0360-3016
Publisher: Elsevier
Journal / Book Title: International Journal of Radiation Oncology - Biology - Physics
Copyright Statement: © 2019 Elsevier Inc. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: Cancer Research UK
Breast Cancer Now
Breast Cancer Now
Medical Research Council (MRC)
Funder's Grant Number: C37/A12011
2012NovemberPhD016
2012MayPR070
MR/N012097/1
Keywords: CRISPR
Colorectal cancer
Mass cytometry
Radioresistance
RhoB
1103 Clinical Sciences
1112 Oncology and Carcinogenesis
0299 Other Physical Sciences
Oncology & Carcinogenesis
Publication Status: Published online
Embargo Date: 2020-04-27
Online Publication Date: 2019-04-27
Appears in Collections:Division of Surgery
Division of Cancer



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