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

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
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.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 9/2015

01-09-2015 | Original Article

High Expression of GRP78 Promotes Invasion and Metastases in Patients with Esophageal Squamous Cell Carcinoma

Authors: Guohong Zhao, Jianqin Kang, Kai Jiao, Guanghui Xu, Lei Yang, Shanhong Tang, Hui Zhang, Ying Wang, Yongzhan Nie, Kaichun Wu, Daiming Fan, Hongbo Zhang, Dexin Zhang

Published in: Digestive Diseases and Sciences | Issue 9/2015

Login to get access

Abstract

Background

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to its high frequency of metastasis and invasion. Recent studies have suggested glucose-regulated protein 78KD (GRP78) may play important roles in progression and development of malignant tumors. However, the mechanisms of invasion and metastasis of ESCC in relation to GRP78 still remain obscure.

Aim

The aim of this study was to investigate the effect of GRP78 on invasion and metastasis of ESCC and to explore its potential mechanism.

Methods

GRP78 expression levels in ESCC tissues were examined by immunohistochemistry. RT-PCR and western blot were used to test the relative expression of GRP78 in non-metastatic and high-metastatic ESCC cells. In vitro and in vivo studies were both performed to investigate the role of GRP78 in invasion and metastasis of ESCC cells. The expression of metastasis-related proteins was examined by western blot in GRP78-depleted cells.

Results

The expression of GRP78 is correlated with invasion, metastasis and poor prognosis in ESCC patients. GRP78 expression was significantly higher in highly metastatic cells compared with ESCC non-metastatic cells. In addition, down-regulation of GRP78 significantly inhibited the metastatic potential of ESCC cells in both in vitro and in vivo studies. The expression of MMP-2 and MMP-9 were down-regulated in GRP78-depleted ESCC cells.

Conclusions

The present study demonstrated that GRP78 plays important roles in invasion and metastasis of ESCC, indicating that GRP78 might be used as a potential prognostic and therapeutic marker in patients with ESCC by modulating the expression of MMP-2 and MMP-9.
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
2.
Eloubeidi MA, Desmond R, Arguedas MR, Reed CE, Wilcox CM. Prognostic factors for the survival of patients with esophageal carcinoma in the US: the importance of tumor length and lymph node status. Cancer. 2002;95:1434–1443.CrossRefPubMed
3.
Lin DC, Du XL, Wang MR. Protein alterations in ESCC and clinical implications: a review. Dis Esophagus. 2009;22:9–20.CrossRefPubMed
4.
Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin N Am. 2005;85:539–553.CrossRefPubMed
5.
Ye Q, Yan Z, Liao X, et al. Muc1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13. Lab Invest. 2011;91:778–787.CrossRefPubMed
6.
Koyama H, Iwata H, Kuwabara Y, Iwase H, Kobayashi S, Fujii Y. Gelatinolytic activity of matrix metalloproteinase-2 and -9 in oesophageal carcinoma. A study using in situ zymography. Eur J Cancer. 2000;36:2164–2170.CrossRefPubMed
7.
Uchikado Y, Natsugoe S, Okumura H, et al. Slug expression in the e-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 2005;11:1174–1180.PubMed
8.
Cao J, Chiarelli C, Richman O, Zarrabi K, Kozarekar P, Zucker S. Membrane type 1 matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer. J Biol Chem. 2008;283:6232–6240.CrossRefPubMed
9.
10.
Xing X, Lai M, Wang Y, Xu E, Huang Q. Overexpression of glucose-regulated protein 78 in colon cancer. Clin Chim Acta. 2006;364:308–315.CrossRefPubMed
11.
Uramoto H, Sugio K, Oyama T, et al. Expression of endoplasmic reticulum molecular chaperone GRP78 in human lung cancer and its clinical significance. Lung Cancer. 2005;49:55–62.CrossRefPubMed
12.
Zhang J, Jiang Y, Jia Z, et al. Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer. Clin Exp Metastasis. 2006;23:401–410.CrossRefPubMed
13.
Daneshmand S, Quek ML, Lin E, et al. Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival. Hum Pathol. 2007;38:1547–1552.CrossRefPubMed
14.
Du XL, Hu H, Lin DC, et al. Proteomic profiling of proteins dysregulted in chinese esophageal squamous cell carcinoma. J Mol Med (Berl). 2007;85:863–875.CrossRef
15.
Dong D, Stapleton C, Luo B, et al. A critical role for GRP78/bip in the tumor microenvironment for neovascularization during tumor growth and metastasis. Cancer Res. 2011;71:2848–2857.PubMedCentralCrossRefPubMed
16.
Li H, Song H, Luo J, Liang J, Zhao S, Su R. Knockdown of glucose-regulated protein 78 decreases the invasion, metalloproteinase expression and ECM degradation in hepatocellular carcinoma cells. J Exp Clin Cancer Res. 2012;31:39.PubMedCentralCrossRefPubMed
17.
Kraljevic PS, Sedic M, Bosnjak H, Spaventi S, Pavelic K. Metastasis: new perspectives on an old problem. Mol Cancer. 2011;10:22.CrossRef
18.
Li Z, Li Z. Glucose regulated protein 78: a critical link between tumor microenvironment and cancer hallmarks. Biochim Biophys Acta. 2012;1826:13–22.PubMed
19.
Dong D, Ni M, Li J, et al. Critical role of the stress chaperone GRP78/bip in tumor proliferation, survival, and tumor angiogenesis in transgene-induced mammary tumor development. Cancer Res. 2008;68:498–505.CrossRefPubMed
20.
Baumeister P, Dong D, Fu Y, Lee AS. Transcriptional induction of GRP78/bip by histone deacetylase inhibitors and resistance to histone deacetylase inhibitor-induced apoptosis. Mol Cancer Ther. 2009;8:1086–1094.PubMedCentralCrossRefPubMed
21.
Zhang LC, Wang JR, Zhao L, et al. GRP78 upregulation-induced increase in cisplatin sensitivity of spca1 lung cancer cells. Chin Med J (Engl). 2011;124:3341–3346.
22.
Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12:895–904.CrossRefPubMed
23.
Zucker S, Vacirca J. Role of matrix metalloproteinases (MMPS) in colorectal cancer. Cancer Metastasis Rev. 2004;23:101–117.CrossRefPubMed
24.
Pellikainen JM, Ropponen KM, Kataja VV, Kellokoski JK, Eskelinen MJ, Kosma VM. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, her2, and prognosis. Clin Cancer Res. 2004;10:7621–7628.CrossRefPubMed
25.
Li Y, Ma J, Guo Q, et al. Overexpression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma. Dis Esophagus. 2009;22:664–667.CrossRefPubMed
Metadata
Title
High Expression of GRP78 Promotes Invasion and Metastases in Patients with Esophageal Squamous Cell Carcinoma
Authors
Guohong Zhao
Jianqin Kang
Kai Jiao
Guanghui Xu
Lei Yang
Shanhong Tang
Hui Zhang
Ying Wang
Yongzhan Nie
Kaichun Wu
Daiming Fan
Hongbo Zhang
Dexin Zhang
Publication date
01-09-2015
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 9/2015
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3689-6

Other articles of this Issue 9/2015

Digestive Diseases and Sciences 9/2015 Go to the issue

Original Article

Characterization of Gastric Cardia Tumors: Differences in Helicobacter pylori Strains and Genetic Polymorphisms

Editorial

Small Intestinal Multifocal Stenosing Ulceration

Stanford Multidisciplinary Seminars

Radiation-Free ERCP in Pregnancy: A “Sound” Approach to Leaving No Stone Unturned

Original Article

Lymph Node Ratio as an Alternative to the Number of Metastatic Lymph Nodes for the Prediction of Esophageal Carcinoma Patient Survival

Correspondence

Are There Any Etiology-Based Specific Findings of Imaging Appearance in Acute Liver Failure?

Original Article

Doppler Ultrasound and Transient Elastography in Liver Transplant Patients for Noninvasive Evaluation of Liver Fibrosis in Comparison with Histology: A Prospective Observational Study
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

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

Read more

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
Image Credits