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)
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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 |
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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 Horgan, Professor Paul and McMillan, Professor Donald and Roseweir, Dr Antonia and Edwards, Professor Joanne and Powell, Dr Arfon 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 > School 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 |
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