Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 12/2016

01-12-2016 | Original Article – Cancer Research

Cytokeratin 18 knockdown decreases cell migration and increases chemosensitivity in non-small cell lung cancer

Authors: Bin Zhang, Jun Wang, Weiran Liu, Yuesong Yin, Dong Qian, Hua Zhang, Bowen Shi, Chenguang Li, Jinfang Zhu, Lianmin Zhang, Liuwei Gao, Changli Wang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2016

Login to get access

Abstract

Purpose

Cytokeratin 18 (CK18) is a structural protein that is normally expressed in many single-layer epithelia. Previous studies have indicated that aberrant CK18 expression is associated with cancer progression. However, the functions of CK18 in lung cancer have not been fully elucidated. Here, we investigate the roles of CK18 in non-small cell lung cancer (NSCLC).

Methods

CK18 protein expression was evaluated by immunohistochemistry in a lung cancer tissue microarray containing 129 cancer samples, and correlations between CK18 expression and clinicopathological characteristics and prognosis were analyzed. We then studied the effects of CK18 knockdown on cell motility and chemosensitivity in lung cancer cells.

Results

High CK18 expression was detected in 101/129 (78.3 %) lung cancers. CK18 expression was significantly correlated to clinical stage, lymph node metastasis, the number of pathologically positive lymph nodes and recurrence and metastasis. Kaplan–Meier survival analysis showed that CK18 was a prognostic factor for overall survival (P = 0.016) and disease-free survival (P = 0.014). In addition, CK18 knockdown decreased cell migration and enhanced the sensitivity of lung cancer cells to paclitaxel.

Conclusions

These findings indicate that CK18 plays an important role in lung cancer progression and may be a therapeutic target for NSCLC.
Literature
go back to reference Chen Y, Cui T, Yang L, Mireskandari M, Knoesel T, Zhang Q, Pacyna-Gengelbach M, Petersen I (2011) The diagnostic value of cytokeratin 5/6, 14, 17, and 18 expression in human non-small cell lung cancer. Oncology 80:333–340. doi:10.1159/000329098 CrossRefPubMed Chen Y, Cui T, Yang L, Mireskandari M, Knoesel T, Zhang Q, Pacyna-Gengelbach M, Petersen I (2011) The diagnostic value of cytokeratin 5/6, 14, 17, and 18 expression in human non-small cell lung cancer. Oncology 80:333–340. doi:10.​1159/​000329098 CrossRefPubMed
go back to reference Chu PG, Weiss LM (2002) Keratin expression in human tissues and neoplasms. Histopathology 40:403–439CrossRefPubMed Chu PG, Weiss LM (2002) Keratin expression in human tissues and neoplasms. Histopathology 40:403–439CrossRefPubMed
go back to reference Coulombe PA, Omary MB (2002) ‘Hard’ and ‘soft’ principles defining the structure, function and regulation of keratin intermediate filaments. Curr Opin Cell Biol 14:110–122CrossRefPubMed Coulombe PA, Omary MB (2002) ‘Hard’ and ‘soft’ principles defining the structure, function and regulation of keratin intermediate filaments. Curr Opin Cell Biol 14:110–122CrossRefPubMed
go back to reference Fuchs E, Cleveland DW (1998) A structural scaffolding of intermediate filaments in health and disease. Science 279:514–519CrossRefPubMed Fuchs E, Cleveland DW (1998) A structural scaffolding of intermediate filaments in health and disease. Science 279:514–519CrossRefPubMed
go back to reference Knosel T, Emde V, Schluns K, Schlag PM, Dietel M, Petersen I (2006) Cytokeratin profiles identify diagnostic signatures in colorectal cancer using multiplex analysis of tissue microarrays. Cell Oncol 28:167–175PubMedPubMedCentral Knosel T, Emde V, Schluns K, Schlag PM, Dietel M, Petersen I (2006) Cytokeratin profiles identify diagnostic signatures in colorectal cancer using multiplex analysis of tissue microarrays. Cell Oncol 28:167–175PubMedPubMedCentral
go back to reference Makino T, Yamasaki M, Takeno A, Shirakawa M, Miyata H, Takiguchi S, Nakajima K, Fujiwara Y, Nishida T, Matsuura N, Mori M, Doki Y (2009) Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. Br J Cancer 101:1298–1306. doi:10.1038/sj.bjc.6605313 CrossRefPubMedPubMedCentral Makino T, Yamasaki M, Takeno A, Shirakawa M, Miyata H, Takiguchi S, Nakajima K, Fujiwara Y, Nishida T, Matsuura N, Mori M, Doki Y (2009) Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. Br J Cancer 101:1298–1306. doi:10.​1038/​sj.​bjc.​6605313 CrossRefPubMedPubMedCentral
go back to reference Messai Y, Noman MZ, Derouiche A, Kourda N, Akalay I, Hasmim M, Stasik I, Ben Jilani S, Chebil M, Caignard A, Azzarone B, Gati A, Ben Ammar Elgaaied A, Chouaib S (2010) Cytokeratin 18 expression pattern correlates with renal cell carcinoma progression: relationship with Snail. Int J Oncol 36:1145–1154PubMed Messai Y, Noman MZ, Derouiche A, Kourda N, Akalay I, Hasmim M, Stasik I, Ben Jilani S, Chebil M, Caignard A, Azzarone B, Gati A, Ben Ammar Elgaaied A, Chouaib S (2010) Cytokeratin 18 expression pattern correlates with renal cell carcinoma progression: relationship with Snail. Int J Oncol 36:1145–1154PubMed
go back to reference Nagashio R, Sato Y, Matsumoto T, Kageyama T, Satoh Y, Ryuge S, Masuda N, Jiang SX, Okayasu I (2010) Significant high expression of cytokeratins 7, 8, 18, 19 in pulmonary large cell neuroendocrine carcinomas, compared to small cell lung carcinomas. Pathol Int 60:71–77. doi:10.1111/j.1440-1827.2009.02487.x CrossRefPubMed Nagashio R, Sato Y, Matsumoto T, Kageyama T, Satoh Y, Ryuge S, Masuda N, Jiang SX, Okayasu I (2010) Significant high expression of cytokeratins 7, 8, 18, 19 in pulmonary large cell neuroendocrine carcinomas, compared to small cell lung carcinomas. Pathol Int 60:71–77. doi:10.​1111/​j.​1440-1827.​2009.​02487.​x CrossRefPubMed
go back to reference Toivola DM, Nieminen MI, Hesse M, He T, Baribault H, Magin TM, Omary MB, Eriksson JE (2001) Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18. Hepatology 34:1174–1183. doi:10.1053/jhep.2001.29374 CrossRefPubMed Toivola DM, Nieminen MI, Hesse M, He T, Baribault H, Magin TM, Omary MB, Eriksson JE (2001) Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18. Hepatology 34:1174–1183. doi:10.​1053/​jhep.​2001.​29374 CrossRefPubMed
go back to reference Woelfle U, Sauter G, Santjer S, Brakenhoff R, Pantel K (2004) Down-regulated expression of cytokeratin 18 promotes progression of human breast cancer. Clin Cancer Res 10:2670–2674CrossRefPubMed Woelfle U, Sauter G, Santjer S, Brakenhoff R, Pantel K (2004) Down-regulated expression of cytokeratin 18 promotes progression of human breast cancer. Clin Cancer Res 10:2670–2674CrossRefPubMed
Metadata
Title
Cytokeratin 18 knockdown decreases cell migration and increases chemosensitivity in non-small cell lung cancer
Authors
Bin Zhang
Jun Wang
Weiran Liu
Yuesong Yin
Dong Qian
Hua Zhang
Bowen Shi
Chenguang Li
Jinfang Zhu
Lianmin Zhang
Liuwei Gao
Changli Wang
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 12/2016
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-016-2253-x

Other articles of this Issue 12/2016

Journal of Cancer Research and Clinical Oncology 12/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.