Type

Journal Article

Authors

Elizabeth J Ryan
Glen A. Dohert
Kieran Sheahan
Jacintha O'Sullivan
Charles S Craik
David Fennelly
Robert Power
Simon Furney
Bláthnaid Nolan
Fiona O'Neill
and 8 others

Subjects

Biochemistry

Topics
tumorigenesis colorectal cancer cancer cell kh type splicing regulatory protein khsrp tumor microenvironment immunology inflammation infection cell growth colorectal cancer crc

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment (2019)

Abstract KH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein implicated in key aspects of cancer cell biology: inflammation and cell-fate determination. However, the role KHSRP plays in colorectal cancer (CRC) tumorigenesis remains largely unknown. Using a combination of in silico analysis of large data sets, ex vivo analysis of protein expression in patients, and mechanistic studies using in vitro models of CRC, we investigated the oncogenic role of KHSRP. We demonstrated KHSRP expression in the epithelial and stromal compartments of both primary and metastatic tumors. Elevated expression was found in tumor versus matched normal tissue, and these findings were validated in larger independent cohorts in silico. KHSRP expression was a prognostic indicator of worse overall survival (hazard ratio, 3.74; 95% CI, 1.43–22.97; P = 0.0138). Mechanistic data in CRC cell line models supported a role of KHSRP in driving epithelial cell proliferation in both a primary and metastatic setting, through control of the G1/S transition. In addition, KHSRP promoted a proangiogenic extracellular environment by regulating the secretion of oncogenic proteins involved in diverse cellular processes, such as migration and response to cellular stress. Our study provides novel mechanistic insight into the tumor-promoting effects of KHSRP in CRC.
Collections Ireland -> Trinity College Dublin -> RSS Feeds
Ireland -> Trinity College Dublin -> Clinical Medicine
Ireland -> Trinity College Dublin -> Clinical Medicine (Scholarly Publications)
Ireland -> Trinity College Dublin -> RSS Feeds
Ireland -> Trinity College Dublin -> School of Medicine

Full list of authors on original publication

Elizabeth J Ryan, Glen A. Dohert, Kieran Sheahan, Jacintha O'Sullivan, Charles S Craik, David Fennelly, Robert Power, Simon Furney, Bláthnaid Nolan, Fiona O'Neill and 8 others

Experts in our system

1
Elizabeth J Ryan
University College Dublin
 
2
Kieran Sheahan
University College Dublin
Total Publications: 40
 
3
Jacintha O'Sullivan
Trinity College Dublin
Total Publications: 74
 
4
David Fennelly
Trinity College Dublin
Total Publications: 11
 
5
Robert Power
Maynooth University
Total Publications: 6
 
6
Simon Furney
Dublin City University
Total Publications: 3
 
7
Blathnaid Nolan
Trinity College Dublin
Total Publications: 8
 
8
Fiona O'Neill
Dublin City University
Total Publications: 7