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01-05-2018 | Original Article

LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer progression and chemoresistance

Authors: Helen Aggelou, Panagiota Chadla, Sofia Nikou, Sofia Karteri, Ioannis Maroulis, Haralabos P. Kalofonos, Helen Papadaki, Vasiliki Bravou

Published in: Virchows Archiv | Issue 5/2018

Abstract

Cofilin phospho-regulation is important for actin filament turnover and is implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH promote cancer cell invasion and metastasis and represent novel anti-cancer targets. However, little is known regarding LIMK/cofilin and SSH in human colorectal cancer (CRC). In this study, we aimed to address their expression and significance in human CRC. We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT) markers β-catenin, E-cadherin, and ZEB. We show that active cofilin, LIMK1, LIMK2, and SSH1 are overexpressed in human CRC and are associated with tumor progression parameters. SSH1 is an independent predictor of lymph node metastasis by multivariate analysis. LIMK1 and SSH1 expression is also higher in non-responders to chemotherapy, and SSH1 is shown by multivariate analysis to independently predict response of metastatic disease to chemotherapy. Active cofilin, LIMK1, LIMK2, and SSH1 also correlated with the EMT markers examined. In addition, immunofluorescence analysis showed increased expression of active cofilin, LIMK1, LIMK2, and SSH1 in HT29 colon cancer cells resistant to 5-fluorouracil compared to parental HT29 cells. Our results suggest that F-actin regulators LIMK/cofilin pathway and SSH1 are associated with CRC progression and chemoresistance representing promising tumor biomarkers and therapeutic targets in CRC.

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Title: LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer progression and chemoresistance
Authors: Helen Aggelou
Panagiota Chadla
Sofia Nikou
Sofia Karteri
Ioannis Maroulis
Haralabos P. Kalofonos
Helen Papadaki
Vasiliki Bravou
Publication date: 01-05-2018
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 5/2018
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-018-2298-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer progression and chemoresistance

Abstract

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Springer Medicine

Abstract

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