Src family kinases, HCK and FGR, associate with local inflammation and tumour progression in colorectal cancer

Roseweir, A. K. , Powell, A. G.M.T., Horstman, S. L., Inthagard, J., Park, J. A. , McMillan, D. C. , Horgan, P. G. and Edwards, J. (2019) Src family kinases, HCK and FGR, associate with local inflammation and tumour progression in colorectal cancer. Cellular Signalling, 56, pp. 15-22. (doi:10.1016/j.cellsig.2019.01.007) (PMID:30684564)

[img]
Preview
Text
178453.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

866kB

Abstract

Background: In colorectal cancer (CRC), inflammatory responses have been reported to associate with patient survival. However, the specific signalling pathways responsible for regulating inflammatory responses are not clear. Src family kinases (SFKs) impact tumourigenic processes, including inflammation. Methods: The relationship between SFK expression, inflammatory responses and cancer specific survival (CSS) in stage I-III CRC patients was assessed using immunohistochemistry on a 272 patient discovery cohort and an extended 822 patient validation cohort. Results: In the discovery cohort, cytoplasmic FGR associated with improved CSS (P=0.019), with membrane HCK (p=0.093) trending towards poorer CSS. In the validation cohort membrane FGR (p=0.016), membrane HCK (p=0.019), and cytoplasmic HCK (p=0.030) all associated with poorer CSS. Both markers also associated with decreased proliferation and cytotoxic T-lymphocytes (all p<0.05). Furthermore, cytoplasmic HCK was an independent prognostic marker compared to common clinical factors. To assess synergy a combine FGR+HCK score was assessed. The membrane FGR+HCK score strengthened associations with poor prognosis (p=0.006), decreased proliferation (p<0.001) and cytotoxic T-lymphocytes (p<0.001) Conclusions: SFKs associate with prognosis and the local inflammatory response in patients with stage I-III CRC. Active membrane FGR and HCK work in parallel to promote tumour progression and down-regulation of the local inflammatory lymphocytic response.

Item Type:Articles
Additional Information:This work was supported by the Royal College of Physicians and Surgeons of Glasgow Ritchie Fellowship.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Park, Mr James and Edwards, Professor Joanne and Horgan, Professor Paul and Powell, Dr Arfon and Roseweir, Dr Antonia and McMillan, Professor Donald and Inthagard, Jitwadee
Authors: Roseweir, A. K., Powell, A. G.M.T., Horstman, S. L., Inthagard, J., Park, J. A., McMillan, D. C., Horgan, P. G., and Edwards, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Cellular Signalling
Publisher:Elsevier
ISSN:0898-6568
ISSN (Online):1873-3913
Published Online:23 January 2019
Copyright Holders:Copyright © 2019 Elsevier Inc.
First Published:First published in Cellular Signalling 56:15-22
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record