Skip to main content
Top
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Hornerin promotes tumor progression and is associated with poor prognosis in hepatocellular carcinoma

Authors: Shun-Jun Fu, Shun-Li Shen, Shao-Qiang Li, Yun-Peng Hua, Wen-Jie Hu, BeiChu Guo, Bao-Gang Peng

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

The function of hornerin (HRNR), a member of the S100 protein family, is poorly clarified in the development of human tumors. The role of HRNR in hepatocellular carcinoma (HCC) progression is investigated in the study.

Methods

The expression levels of HRNR were assessed in tumor samples from a cohort of 271 HCC patients. The effect of HRNR on proliferation, colony formation and invasion of tumor cells was examined. We further determined the role of HRNR in tumor growth in vivo by using xenograft HCC tumor models. The possible mechanism of the HRNR promotion of HCC progression was explored.

Results

We found that HRNR was overexpressed in HCC tissues. The high expression of HRNR in HCCs was significantly associated with vascular invasion, poor tumor differentiation, and advanced TNM stage. The disease-free survival (DFS) and overall survival (OS) of HCC patients with high HRNR expression were poorer than those in the low HRNR expression group. HRNR expression was an independent risk factor linked to both poor DFS (HR = 2.209, 95% CI = 1.627–2.998,P <  0.001) and OS (HR = 2.459,95% CI = 1.736–3.484, P <  0.001). In addition, the knockdown of HRNR by shRNAs significantly inhibited the proliferation, colony formation, migration and invasion of HCC tumor cells. HRNR silencing led to the decreased phosphorylation of AKT signaling. Notably, tumor growth was markedly inhibited by HRNR silencing in a xenograft model of HCC.

Conclusions

HRNR promotes tumor progression and is correlated with a poor HCC prognosis. HRNR may contribute to HCC progression via the regulation of the AKT pathway.
Literature
2.
go back to reference Srikrishna G, Freeze HH. Endogenous damage-associated molecular pattern molecules at the crossroads of inflammation and cancer. Neoplasia. 2009;11:615–28.CrossRefPubMedPubMedCentral Srikrishna G, Freeze HH. Endogenous damage-associated molecular pattern molecules at the crossroads of inflammation and cancer. Neoplasia. 2009;11:615–28.CrossRefPubMedPubMedCentral
3.
go back to reference Makino T, Takaishi M, Morohashi M, Huh NH. Hornerin, a novel profilaggrin-like protein and differentiation -specific marker isolated from mouse skin. J Biol Chem. 2001;276:47445–52.CrossRefPubMed Makino T, Takaishi M, Morohashi M, Huh NH. Hornerin, a novel profilaggrin-like protein and differentiation -specific marker isolated from mouse skin. J Biol Chem. 2001;276:47445–52.CrossRefPubMed
4.
go back to reference McKiernan E, McDermott EW, Evoy D, Crown J, Duffy MJ. The role of S100 genes in breast cancer progression. Tumour Biol. 2011;32:441–50.CrossRefPubMed McKiernan E, McDermott EW, Evoy D, Crown J, Duffy MJ. The role of S100 genes in breast cancer progression. Tumour Biol. 2011;32:441–50.CrossRefPubMed
5.
go back to reference Zhang H, Liu J, Yue D, Gao L, Wang D, Zhang H, et al. Clinical significance of E-cadherin, β-catenin, vimentin and S100A4 expression in completely resected squamous cell lung carcinoma. J Clin Pathol. 2013;66:937–45.CrossRefPubMed Zhang H, Liu J, Yue D, Gao L, Wang D, Zhang H, et al. Clinical significance of E-cadherin, β-catenin, vimentin and S100A4 expression in completely resected squamous cell lung carcinoma. J Clin Pathol. 2013;66:937–45.CrossRefPubMed
6.
go back to reference Saleem M, Kweon MH, Johnson JJ, Adhami VM, Elcheva I, Khan N, et al. S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9. Proc Natl Acad Sci U S A. 2006;103:14825–30.CrossRefPubMedPubMedCentral Saleem M, Kweon MH, Johnson JJ, Adhami VM, Elcheva I, Khan N, et al. S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9. Proc Natl Acad Sci U S A. 2006;103:14825–30.CrossRefPubMedPubMedCentral
7.
go back to reference Liu H, Wang L, Wang X, Cao Z, Yang Q, Zhang K. S100A7 enhances invasion of human breast cancer MDA-MB-468 cells through activation of nuclear factor-κB signaling. World J Surg Oncol. 2013;11:1–8.CrossRef Liu H, Wang L, Wang X, Cao Z, Yang Q, Zhang K. S100A7 enhances invasion of human breast cancer MDA-MB-468 cells through activation of nuclear factor-κB signaling. World J Surg Oncol. 2013;11:1–8.CrossRef
9.
go back to reference Shen SL, Qiu FH, Dayarathna TK, Wu J, Kuang M, Li SS, et al. Identification of Dermcidin as a novel binding protein of Nck1 and characterization of its role in promoting cell migration. Biochim Biophys Acta. 1812;2011:703–10. Shen SL, Qiu FH, Dayarathna TK, Wu J, Kuang M, Li SS, et al. Identification of Dermcidin as a novel binding protein of Nck1 and characterization of its role in promoting cell migration. Biochim Biophys Acta. 1812;2011:703–10.
10.
go back to reference Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.CrossRefPubMed Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.CrossRefPubMed
11.
go back to reference Fu SJ, Qi CY, Xiao WK, Li SQ, Peng BG, Liang LJ. Glypican-3 is a potential prognostic biomarker for hepatocellular carcinoma after curative resection. Surgery. 2013;154:536–44.CrossRefPubMed Fu SJ, Qi CY, Xiao WK, Li SQ, Peng BG, Liang LJ. Glypican-3 is a potential prognostic biomarker for hepatocellular carcinoma after curative resection. Surgery. 2013;154:536–44.CrossRefPubMed
12.
go back to reference Fu SJ, Shen SL, Li SQ, Hua YP, Liang LJ, Peng BG. Prognostic value of preoperative peripheral neutrophil-to-lymphocyte ratio in patients with HBV- associated hepatocellular carcinoma after radical hepatectomy. Med Oncol. 2013;30:721.CrossRefPubMed Fu SJ, Shen SL, Li SQ, Hua YP, Liang LJ, Peng BG. Prognostic value of preoperative peripheral neutrophil-to-lymphocyte ratio in patients with HBV- associated hepatocellular carcinoma after radical hepatectomy. Med Oncol. 2013;30:721.CrossRefPubMed
13.
go back to reference Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G, et al. A lentiviral RNA library for human and mouse genes applied to an arrayed viral high-content screen. Cell. 2006;124:1283–98.CrossRefPubMed Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G, et al. A lentiviral RNA library for human and mouse genes applied to an arrayed viral high-content screen. Cell. 2006;124:1283–98.CrossRefPubMed
14.
go back to reference Dai Z, Zhou SL, Zhou ZJ, Bai DS, Xu XY, Fu XT, et al. Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signaling pathways. J Pathol. 2014;234:316–28.CrossRefPubMed Dai Z, Zhou SL, Zhou ZJ, Bai DS, Xu XY, Fu XT, et al. Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signaling pathways. J Pathol. 2014;234:316–28.CrossRefPubMed
15.
go back to reference Sarela AI, Scott N, Ramsdale J, Markham AF, Guillou PJ. Immunohistochemical detection of the anti-apoptosis protein, survivin, predicts survival after curative resection of stage II colorectal carcinomas. Ann Surg Oncol. 2001;8:305–10.CrossRefPubMed Sarela AI, Scott N, Ramsdale J, Markham AF, Guillou PJ. Immunohistochemical detection of the anti-apoptosis protein, survivin, predicts survival after curative resection of stage II colorectal carcinomas. Ann Surg Oncol. 2001;8:305–10.CrossRefPubMed
16.
go back to reference Li Y, Liang Q, Wen YQ, Chen LL, Wang LT, Liu YL, et al. Comparative proteomics analysis of human osteosarcomas and benign tumor of bone. Cancer Genet Cytogenet. 2010;198:97–106.CrossRefPubMed Li Y, Liang Q, Wen YQ, Chen LL, Wang LT, Liu YL, et al. Comparative proteomics analysis of human osteosarcomas and benign tumor of bone. Cancer Genet Cytogenet. 2010;198:97–106.CrossRefPubMed
17.
go back to reference Huang B, Cao KY, Li XB, Guo SJ, Mao XP, Wang Z, et al. The expression and role of protein kinase C (PKC) epsilon in clear cell renal cell carcinoma. J Exp Clin Cancer Res. 2011;30:88.CrossRefPubMedPubMedCentral Huang B, Cao KY, Li XB, Guo SJ, Mao XP, Wang Z, et al. The expression and role of protein kinase C (PKC) epsilon in clear cell renal cell carcinoma. J Exp Clin Cancer Res. 2011;30:88.CrossRefPubMedPubMedCentral
18.
go back to reference Zhu W, Xue Y, Liang C, Zhang R, Zhang Z, Li H, et al. S100A16 promotes cell proliferation and metastasis via AKT and ERK cell signaling pathways in human prostate cancer. Tumour Biol. 2016;37:12241–50.CrossRefPubMed Zhu W, Xue Y, Liang C, Zhang R, Zhang Z, Li H, et al. S100A16 promotes cell proliferation and metastasis via AKT and ERK cell signaling pathways in human prostate cancer. Tumour Biol. 2016;37:12241–50.CrossRefPubMed
19.
go back to reference Zhang K, Zhang M, Zhao H, Yan B, Zhang D, Liang J. S100A4 regulates motility and invasiveness of human esophageal squamous cell carcinoma through modulating the AKT/slug signal pathway. Dis Esophagus. 2012;25:731–9.CrossRefPubMed Zhang K, Zhang M, Zhao H, Yan B, Zhang D, Liang J. S100A4 regulates motility and invasiveness of human esophageal squamous cell carcinoma through modulating the AKT/slug signal pathway. Dis Esophagus. 2012;25:731–9.CrossRefPubMed
20.
go back to reference Afanador L, Roltsch EA, Holcomb L, Campbell KS, Keeling DA, Zhang Y, et al. The Ca2+ sensor S100A1 modulates neuroinflammation, histopathology and Akt activity in the PSAPP Alzheimer's disease mouse model. Cell Calcium. 2014;56:68–80.CrossRefPubMed Afanador L, Roltsch EA, Holcomb L, Campbell KS, Keeling DA, Zhang Y, et al. The Ca2+ sensor S100A1 modulates neuroinflammation, histopathology and Akt activity in the PSAPP Alzheimer's disease mouse model. Cell Calcium. 2014;56:68–80.CrossRefPubMed
21.
go back to reference Wang G, Rudland PS, White MR, Barraclough R. Interaction in vivo and in vitro of the metastasis-inducing S100 protein, S100A4 (p9Ka) with S100A1. J Biol Chem. 2000;275:11141–6.CrossRefPubMed Wang G, Rudland PS, White MR, Barraclough R. Interaction in vivo and in vitro of the metastasis-inducing S100 protein, S100A4 (p9Ka) with S100A1. J Biol Chem. 2000;275:11141–6.CrossRefPubMed
22.
go back to reference Leclerc E, Heizmann CW. The importance of Ca2+/Zn2+ signaling S100 proteins and RAGE in translational medicine. Front Biosci (Schol Ed). 2011;3:1232–62. Leclerc E, Heizmann CW. The importance of Ca2+/Zn2+ signaling S100 proteins and RAGE in translational medicine. Front Biosci (Schol Ed). 2011;3:1232–62.
23.
go back to reference Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 2003;4:517–29.CrossRefPubMed Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 2003;4:517–29.CrossRefPubMed
25.
go back to reference Fleming JM, Ginsburg E, Oliver SD, Goldsmith P, Vonderhaar BK. Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer. BMC Cancer. 2012;12:266.CrossRefPubMedPubMedCentral Fleming JM, Ginsburg E, Oliver SD, Goldsmith P, Vonderhaar BK. Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer. BMC Cancer. 2012;12:266.CrossRefPubMedPubMedCentral
26.
27.
go back to reference Mayer IA, Arteaga CL. The PI3K/AKT pathway as a target for Cancer treatment. Annu Rev Med. 2016;67:11–28.CrossRefPubMed Mayer IA, Arteaga CL. The PI3K/AKT pathway as a target for Cancer treatment. Annu Rev Med. 2016;67:11–28.CrossRefPubMed
28.
go back to reference Dobashi Y, Sato E, Oda Y, Inazawa J, Ooi A. Significance of Akt activation and AKT gene increases in soft tissue tumors. Hum Pathol. 2014;45:127–36.CrossRefPubMed Dobashi Y, Sato E, Oda Y, Inazawa J, Ooi A. Significance of Akt activation and AKT gene increases in soft tissue tumors. Hum Pathol. 2014;45:127–36.CrossRefPubMed
30.
Metadata
Title
Hornerin promotes tumor progression and is associated with poor prognosis in hepatocellular carcinoma
Authors
Shun-Jun Fu
Shun-Li Shen
Shao-Qiang Li
Yun-Peng Hua
Wen-Jie Hu
BeiChu Guo
Bao-Gang Peng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4719-5

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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