Top

Published in:

Open Access 01-03-2016 | Original Article

Overexpression of acylglycerol kinase is associated with poorer prognosis and lymph node metastasis in nasopharyngeal carcinoma

Authors: Qian Zhu, Su-Mei Cao, Huan-Xin Lin, Qi Yang, Sai-Lan Liu, Ling Guo

Published in: Tumor Biology | Issue 3/2016

Abstract

Acylglycerol kinase (AGK) has been reported to promote a malignant phenotype and enhance the development of cancer stem cells. However, the clinical value of AGK in cancer remains unclear. This study aimed to investigate the expression and clinicopathological significance of AGK in nasopharyngeal carcinoma (NPC). AGK was significantly upregulated in NPC cell lines and clinical specimens as indicated by real-time PCR and Western blotting. Among the AGK-positive cases, 52/114 (45.6 %) of the archived human NPC specimens expressed high levels of AGK. High expression of AGK was associated with significantly shorter overall and disease-free survival (P < 0.001 and P = 0.002; log-rank test) and was an independent prognostic factor for overall survival (P = 0.041; multivariate Cox analysis). High AGK expression was associated with lymph node metastasis (P < 0.001; chi-squared test) and was an independent predicted factor for lymph node metastasis in NPC (P = 0.032; multivariate logistic analysis). AGK is overexpressed and associated with disease progression and lymph node metastasis in NPC. AGK has potential as a novel prognostic factor for overall survival in NPC.

Wei KR, Zheng RS, Zhang SW, Liang ZH, Ou ZX, Chen WQ. Nasopharyngeal carcinoma incidence and mortality in China in 2010. Chin J Cancer. 2014;33(8):381–7.PubMedPubMedCentral

Cao SM, Simons MJ, Qian CN. The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer. 2011;30(2):114–9.CrossRefPubMedPubMedCentral

Lo KW, To KF, Huang DP. Focus on nasopharyngeal carcinoma. Cancer Cell. 2004;5(5):423–8.CrossRefPubMed

Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1765–77.CrossRefPubMed

Suárez C, Rodrigo JP, Rinaldo A, Langendijk JA, Shaha AR, Ferlito A. Current treatment options for recurrent nasopharyngeal cancer. Eur Arch Otorhinolaryngol. 2010;267(12):1811–24.CrossRefPubMedPubMedCentral

Farias TP, Dias FL, Lima RA, Kligerman J, de Sá GM, Barbosa MM, et al. Prognostic factors and outcome for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2003;129(7):794–9.CrossRefPubMed

Qi S, Chunying S, Lin K, Xiaoshen W, Jianhui D, Yunsheng G, et al. Involvement of both cervical lymph nodes and retropharyngeal lymph nodes has prognostic value for N1 patients with nasopharyngeal carcinoma. Radiat Oncol. 2014;9:7.CrossRef

Bektas M, Payne SG, Liu H, Goparaju S, Milstien S, Spiegel S. A novel acylglycerol kinase that produces lysophosphatidic acid modulates cross talk with EGFR in prostate cancer cells. J Cell Biol. 2005;169(5):801–11.CrossRefPubMedPubMedCentral

Epand RM, Shulga YV, Timmons HC, Perri AL, Belani JD, Perinpanathan K, et al. Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. Biochemistry. 2007;46(49):14225–31.CrossRefPubMed

10.

Zhao Y, Natarajan V. Lysophosphatidic acid signaling in airway epithelium: role in airway inflammation and remodeling. Cell Signal. 2009;21(3):367–77.CrossRefPubMed

11.

Kalari S, Zhao Y, Spannhake EW, Berdyshev EV, Natarajan V. Role of acylglycerol kinase in LPA-induced IL-8 secretion and transactivation of epidermal growth factor-receptor in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2009;296(3):328–36.CrossRef

12.

Mills GB, Moolenaar WH. The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer. 2003;3(8):582–91.CrossRefPubMed

13.

Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, et al. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol. 2002;158(2):227–33.CrossRefPubMedPubMedCentral

14.

Nouh MA, Wu XX, Okazoe H, Hiroyuki T, Reiji H, Abdel Muneem Mohammed A-Z, et al. Expression of autotoxin and acylglycerol kinase in prostate cancer: association with cancer development and progression. Cancer Sci. 2009;100(9):1631–8.CrossRefPubMed

15.

Wang X, Lin C, Zhao X, Liu A, Zhu J, Li X, et al. Acylglycerol kinase promotes cell proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Mol Cancer. 2014;13:106.CrossRefPubMedPubMedCentral

16.

Chen X, Ying Z, Lin X, Lin H, Wu J, Li M, et al. Acylglycerol kinase augments JAK2/STAT3 signaling in esophageal squamous cells. J Clin Invest. 2013;123(6):2576–89.CrossRefPubMedPubMedCentral

17.

Liu G, Ren X, Gao C, Zhang W. Acylglycerol kinase promotes the proliferation and cell cycle progression of oral squamous cell carcinoma. Mol Med Rep. 2015;12(2):2225–30.PubMed

18.

Cui Y, Lin C, Wu Z, Liu A, Zhang X, Zhu J, et al. AGK enhances angiogenesis and inhibits apoptosis via activation of the NF-κB signaling pathway in hepatocellular carcinoma. Oncotarget. 2014;5(23):12057–69.CrossRefPubMedPubMedCentral

19.

Sham JST, Choy D, Wei WI. Nasopharyngeal carcinoma: orderly neck node spread. Int J Radiat Oncol Biol Phys. 1990;19(4):929–33.CrossRefPubMed

20.

Chang-Chuan P, Jin L, Jing-Rui Y, Ping C, Wang L, Zi-lin H, et al. Challenges in the modification of the M1 stage of the TNM staging system for nasopharyngeal carcinoma: A study of 1027 cases and review of the literature. Exp Ther Med. 2012;4(2):334–8.

21.

Lee CC, Chu ST, Chou P, Lee CC, Chen LF. The prognostic influence of prevertebral space involvement in nasopharyngeal carcinoma. Clin Otolaryngol. 2008;33(5):442–9.CrossRefPubMed

22.

Sham JS, Choy D, Wei WI. Nasopharyngeal carcinoma: orderly neck node spread. Int J Radiat Oncol Biol Phys. 1990;19(4):929–33.CrossRefPubMed

23.

Liping L, Lin C, Liang W, Wu S, Liu A, Wu J, et al. TBL1XR1 promotes lymphangiogenesis and lymphatic metastasis in esophageal squamous cell carcinoma. Original Article. 2015;64(1):26–36.

24.

Wakisak N, Hirota K, Kondo S, Sawada-Kitamura S, Endo K, Murono S, et al. Induction of lymphangiogenesis through vascular endothelial growth factor-C/vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma. Oral Oncol. 2012;48(8):703–8.CrossRef

25.

Stacker SA, Achen MG, Jussila L, Baldwin ME, Alitalo K. Lymphangiogenesis and cancer metastasis. Nat Rev Cancer. 2002;2(8):573–83.CrossRefPubMed

26.

Chang W-C, Wu S-L, Huang W-C, Hsu J-Y, Chan S-H, Wang J-M, et al. PTX3 gene activation in EGF-induced head and neck cancer cell metastasis. Oncotarget. 2015;6(10):7741–57.CrossRefPubMedPubMedCentral

27.

Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2(7):489–501.CrossRefPubMed

28.

Tokunaga E, Oki E, Egashira A, Sadanaga N, Morita M, Kakeji Y, et al. Deregulation of the AKT pathway in human cancer. Curr Cancer Drug Targets. 2008;8(1):27–36.CrossRefPubMed

29.

Hui AB, Lo KW, Teo PM, To KF, Huang DP. Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by array based comparative genomic hybridization. Int J Oncol. 2002;20(3):467–73.PubMed

Title: Overexpression of acylglycerol kinase is associated with poorer prognosis and lymph node metastasis in nasopharyngeal carcinoma
Authors: Qian Zhu
Su-Mei Cao
Huan-Xin Lin
Qi Yang
Sai-Lan Liu
Ling Guo
Publication date: 01-03-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4148-x

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

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2016

Differential function and regulation of orphan nuclear receptor TR3 isoforms in endothelial cells

Alanine aminotransferase to hemoglobin ratio is an indicator for disease progression for hepatocellular carcinoma patients receiving transcatheter arterial chemoembolization

SPARCL1 is a novel predictor of tumor recurrence and survival in hilar cholangiocarcinoma

The SDF-1/CXCR4 chemokine axis in uveal melanoma cell proliferation and migration

The clinical significance of systemic inflammation score in esophageal squamous cell carcinoma

Methyl methanesulfonate induces necroptosis in human lung adenoma A549 cells through the PIG-3-reactive oxygen species pathway

Keynote webinar | Spotlight on antibody–drug conjugates in cancer