Received: 5 June 2017
Accepted: 20 July 2017
DOI: 10.1002/pro6.22
REVIEW
Fascin and esophageal squamous cell carcinoma Yinwei Cheng1,2 Zepeng Du1,4 Xiu-e Xu1,2
Feng Pan1,3 Liandi Liao1,2
Yuhui Peng1,7 Junhui Fu6
Jianjun Xie1,3
Famin Zeng1,3
Jianyi Wu1,3 Yangmin Xie1,5
Yiwei Xu1,7
Lei Xie1,3
Lihua Tao1,2
Bingli Wu1,3
Pixian Zhang1,3
Jian Shen1,2
Wenming Xie1,8
Chunpeng Zheng6
Pingjuan Nie1,3
Zhiyong Wu6
Shaohong Wang4 Wangkai Fang1,3
Xuanhao Lin4 Liyan Xu1,2 β
Enmin Li1,3 1 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, China 2 Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, China 3 Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, China 4 Departments of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong, China 5 Laboratory Animal Center, Shantou University Medical College, Shantou, Guangdong, China 6 Departments of Oncology Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong, China 7 Department of Clinical Laboratory, Cancer Hospital, Shantou University Medical College, Shantou, China 8 Medical Bioinformatics Center, Shantou University Medical College, Shantou, Guangdong, China
Correspondence Enmin Li, The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China. Email:
[email protected] Funding Information Natural Science Foundation of China-Guangdong Joint Key Fund, Grant Numbers U1301227 and U0932001; National Natural Science Foundation of China, Grant Numbers 81472613 and 81172264 β Additional correspondence
Liyan Xu Email:
[email protected]
Abstract In a cancer prevalence survey, China was recognized to have a high incidence of esophageal cancer. Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer and accounts for the vast majority of cases every year. ESCC cases in China contribute toward nearly half of all new global cases each year. As one of the higher ESCC prevalence regions in China, the Chaoshan District of Guangdong Province is the only area on the Chinese coastline with such a distinguished profile. Our laboratory, which is located in the Chaoshan District, studies the biological function, molecular basis, regulation mechanisms, and clinical significance of abnormally expressed cellular cytoskeleton binding proteins in ESCC, such as ezrin, fascin, LCN2, LOXL2, and DSC2. In the present review, we summarized studies on fascin in ESCC reported by our laboratory and other laboratories around the world. In ESCC, fascin expression is highly upregulated at the mRNA and protein levels, and can serve as an early biomarker for tumor invasion and metastasis. Furthermore, fascin transcription is directly activated through Sp1 binding to its promoter; this process is enhanced through the phosphorylation of Sp1 by the epidermal grown factoractivated Mitogen-activated protein kinase (MAPK)/Extracellular signal-regulated kinase (ERK) (MEK)-ERK1/2 signaling pathway. Furthermore, the function of fascin is also regulated by posttranslational modifications. For instance, the phosphorylation of several amino acid residues of fascin inhibits ESCC cell behavior and filopodia formation. However, whether other types of fascin modifications exist remains unknown and requires further study. KEYWORDS
esophageal squamous cell carcinoma, F-actin, fascin, fascin overexpression, post-translational modification
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. c 2017 The Authors. Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute. Prec. Radiat. Oncol. 2017;1:82β87.
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1
F-actin filaments by two major acting-binding sites. One site is located
INTRODUCTION
around a serine39 near the cleft between π½-trefoil 1 and π½-trefoil 4,20 Because of increasing incidence and mortality, cancer has become a
and the other site is located within residues 277β493, which encom-
major public health problem in China.1 Esophageal cancer (ES) is the
passes most of π½-trefoil 3 and π½-trefoil 4.21 The phosphorylation of
seventh most common cancer worldwide and the sixth most common
residue serine-39 by protein kinase CπΌ has been reported to block the
cause of cancer
death.2
Annually, approximately half of new world-
wide ES cases are diagnosed in China, with esophageal squamous cell
activity of the N-terminal F-actin-bundling site.21,22 However, the regulation of other F-actin-bundling sites has not been well studied.
carcinoma (ESCC) being the most predominant histological subtype, accounting for nearly 90% of all EC.1,3 In China, ESCC cases are geographically distributed in different regions, including the Chaoshan district in Guangdong province, areas of the Taihang Mountains, and
3
ROLES OF FASCIN IN ESCC
in Yanting, the hilly regions of Sichuan Province.4,5 Recent progress in oncology surgical resections and adjuvant chemoradiation has
As an F-actin bundle protein, fascin has been widely shown to reg-
improved the prognosis of ESCC. However, with a 5-year survival
ulate the assembly of F-actin bundles in a variety of different cel-
rate of
