LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer progression and chemoresistance.
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-can...
| Publicado en: | Virchows Archiv: European Journal of Pathology Vol. 472; no. 5; pp. 727 - 738 |
|---|---|
| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
May2018
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=129738543&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 129738543 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09456317 O1Z jtl: Virchows Archiv: European Journal of Pathology issn: 09456317 maglogo: N pubinfo: dt: May2018 vid: 472 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 129738543 129738543 NLM29352327 10.1007/s00428-018-2298-0 NLM29352327 129738543 ppf: 727 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer progression and chemoresistance. aug: au: Aggelou, Helen Chadla, Panagiota Nikou, Sofia Karteri, Sofia Maroulis, Ioannis Kalofonos, Haralabos P. Papadaki, Helen Bravou, Vasiliki affil: Department of Anatomy-Histology-Embryology, Medical School, University of Patras, 26500, Patras, Greece sug: subj: Drug Resistance, Neoplasm Colorectal Neoplasms Pathology Aged Female Esterases Phosphotransferases Aged, 80 and Over Esterases Analysis Adult Microfilament Proteins Analysis Middle Age Antineoplastic Agents, Combined Therapeutic Use Phosphotransferases Analysis Male Signal Transduction Physiology Disease Progression Microfilament Proteins Colorectal Neoplasms Drug Therapy Aged: 65+ years Aged, 80 & over Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|