Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

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.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 4/2014

01-04-2014 | Research Article

Absent expression of FLNA is correlated with poor prognosis of nasopharyngeal cancer

Authors: G. G. Sun, Y. F. Lu, Y. J. Cheng, W. N. Hu

Published in: Tumor Biology | Issue 4/2014

Login to get access

Abstract

This study aimed to analyze the expression, clinical significance of filamin A (FLNA) in nasopharyngeal carcinoma, and the biological effect in its cell line by FLNA overexpression. Immunohistochemistry and western blot were used to analyze FLNA protein expression in 63 cases of nasopharyngeal cancer and 21 cases of normal tissues to study the relationship between FLNA expression and clinical factors. FLNA lentiviral vector and empty vector were respectively transfected into nasopharyngeal cancer CNE2 cell line. Reverse transcription–polymerase chain reaction (RT-PCR) and western blot were used to detect the mRNA level and protein of FLNA. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, migration, and invasion assays were also conducted as to the influence of the upregulated expression of FLNA that might be found on CNE2 cell biological effect. Immunohistochemistry: the level of FLNA protein expression was found to be significantly lower in nasopharyngeal cancer tissue than normal tissues (P < 0.05). Western blot: the relative amount of FLNA protein in nasopharyngeal cancer tissue was found to be significantly lower than in normal tissues (P < 0.05). The level of FLNA protein expression was correlated with T stages, lymph node metastasis, clinic stage, and histological grade (P < 0.05). Loss of FLNA expression correlated significantly with poor overall survival time by Kaplan–Meier analysis (P < 0.05). The result of biological function has shown that CNE2 cell-transfected FLNA had a lower survival fraction, significant decrease in migration and invasion, and lower matrix metallopeptidase 9 (MMP-9) protein expression compared with CNE2 cell-untransfected FLNA (P < 0.05). FLNA expression decreased in nasopharyngeal cancer and correlated significantly lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that FLNA may play important roles as a negative regulator to nasopharyngeal cancer CNE2 cell by promoting degradation of MMP-9.
Literature
1.
2.
Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in nasopharyngeal cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary nasopharyngeal carcinoma. Cancer Res. 2003;63:1454–7.PubMed
3.
Zhou X, Boren J, Akyurek LM. Filamins in cardiovascular development. Trends Cardiovasc Med. 2007;17:222–9.PubMedCrossRef
4.
Ai J, Huang H, Lv X, Tang Z, Chen M, Chen T, et al. FLNA and PGK1 are two potential markers for progression in hepatocellular carcinoma. Cell Physiol Biochem. 2011;27:207–16.PubMedCrossRef
5.
Stossel TP, Condeelis J, Cooley L, Hartwig JH, Noegel A, Schleicher M, et al. Filamins as integrators of cell mechanics and signalling. Nat Rev Mol Cell Biol. 2001;2:138–45.PubMedCrossRef
6.
Sheen VL, Feng Y, Graham D, Takafuta T, Shapiro SS, Walsh CA. Filamin A and filamin B are co-expressed within neurons during periods of neuronal migration and can physically interact. Hum Mol Genet. 2002;11:2845–54.PubMedCrossRef
7.
Feng Y, Walsh CA. The many faces of filamin: a versatile molecular scaffold for cell motility and signalling. Nat Cell Biol. 2004;6:1034–8.PubMedCrossRef
8.
Bedolla RG, Wang Y, Asuncion A, Chamie K, Siddiqui S, Mudryj MM, et al. Nuclear versus cytoplasmic localization of filamin A in prostate cancer: immunohistochemical correlation with metastases. Clin Cancer Res. 2009;15:788–96.PubMedCentralPubMedCrossRef
9.
Bourguignon LY, Gilad E, Peyrollier K. Heregulin-mediated ErbB2-ERK signaling activates hyaluronan synthases leading to CD44-dependent ovarian tumor cell growth and migration. J Biol Chem. 2007;282:19426–41.PubMedCrossRef
10.
11.
Roberson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, et al. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diversem alform at ions in humans. Nat Genet. 2003;33:487–91.CrossRef
12.
Keshamouni VG, Michailidis G, Grasso CS, Anthwal S, Strahler JR, Walker A, et al. Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/ invasive phenotype. J Proteome Res. 2006;5:1143–54.PubMedCrossRef
13.
Shi JW, Yu YM, Wang SJ, Zhang J, Wang GY. Expressions of filamin A and matrix metalloproteinase 9 in colorectal adenocarcinoma and their significance. Tumor. 2010;30:768–73.
14.
Wu YP, Li JB, Zhao RJ, Zhao RJ, Wang XL, Shan BE, et al. Expression of filamin A in invasive breast carcinoma and its significance. Tumor. 2009;29:659–62.
15.
Watanabe H. Extracellular matrix-regulationof cancer invasion and metastasis. Gan ToKagaku Ryoho. 2010;37:2058–61.
16.
Yu HB, Zhang HF, Li DY, Zhang X, Xue HZ, Zhao SH. Matrine inhibits matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells. J Asian Nat Prod Res. 2011;13:242–50.PubMedCrossRef
17.
Zhang M, Zhu GY, Gao HY, Zhao SP, Xue Y. Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in nasopharyngeal adenocarcinoma. J Surg Oncol. 2011;103:243–7.PubMedCrossRef
18.
19.
Onoprishvili I, Ali S, Andria ML, Shpigel A, Simon EJ. Filamin A mutant lacking actin-binding domain restores mu opioid receptor regulation in melanoma cells. Neurochem Res. 2008;33:2054–61.PubMedCrossRef
20.
Zhu TN, He HJ, Kole S, D’Souza T, Agarwal R, Morin PJ, et al. Filamin A-mediated down-regulation of the exchange factor Ras-GRF1 correlates with decreased matrix metalloproteinase-9 expression in human melanoma cells. J Biol Chem. 2007;282:14816–26.PubMedCrossRef
21.
He HJ, Kole S, Kwon YK, Crow MT, Bernier M. Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway. J Biol Chem. 2003;278:27096–104.PubMedCrossRef
Metadata
Title
Absent expression of FLNA is correlated with poor prognosis of nasopharyngeal cancer
Authors
G. G. Sun
Y. F. Lu
Y. J. Cheng
W. N. Hu
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1381-z

Other articles of this Issue 4/2014

Tumor Biology 4/2014 Go to the issue

Research Article

Lack of association between interleukin-4 −524C>T polymorphism and colorectal cancer susceptibility

Research Article

Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma

Research Article

The Arg188His polymorphism in the XRCC2 gene and the risk of cancer

Research Article

The -786T > C polymorphism in the NOS3 gene is associated with increased cancer risk

Research Article

Association between cytotoxic T lymphocyte antigen-4 +49A/G, −1722T/C, and −1661A/G polymorphisms and cancer risk: a meta-analysis

Research Article

Differential association of RANTES-403 and IL-1B-1464 polymorphisms on histological subtypes in male Korean patients with gastric cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits