HSP70/HSP90-Organizing Protein Contributes to Gastric Cancer Progression in an Autocrine Fashion and Predicts Poor Survival in Gastric Cancer

Ertao Zhai, Wei Liang, Yi Lin, Linlin Huang, Xin He, Shirong Cai, Jianhui Chen, Ning Zhang, Jiali Li, Qiuyang Zhang, Yulong He, Zhirong Zeng, Minhu Chen, Lixia Xu, Sui Peng

Research output: Contribution to journalArticle

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Abstract

Background/Aims: HSP70/HSP90-organizing protein (HOP) is an adaptor protein that mediates heat shock protein 70 (HSP70) and HSP90 folding. HOP can be secreted by cancer cells and promote malignant cell growth in an autocrine manner. Here, we studied its role in gastric cancer (GC). Methods: HOP mRNA and protein levels were detected by quantitative real-time PCR and western blotting, respectively, and enzyme-linked immunosorbent assay was used to determine the serum levels. Immunohistochemistry was performed to analyze HOP expression in 117 GC tissues and 32 adjacent normal tissues. The Cell Counting Kit-8 cell viability assay, flow cytometry, and western blotting were used to analyze the effects of HOP on cell proliferation and apoptosis, and the potential underlying mechanisms. Results: HOP mRNA and protein levels were significantly higher in GC tissues than in normal tissues in our medical center (P< 0.001) and in The Cancer Genome Atlas database (P< 0.001). GC patients had higher serum levels of HOP than age-matched healthy controls (P< 0.001); however, once tumors were removed, serum levels significantly decreased (P< 0.01). In human GC tissues, increased HOP expression was associated with tumor progression and poor survival. Notably, autocrine HOP promoted cell proliferation through the phospholipase Cγ1-extracellular signal-regulated kinase 1/2-dependent pathway, and inhibited cell apoptosis by regulating the activities of caspase 9, caspase 3, and B-cell lymphoma 2. Blocking extracellular HOP with neutralizing antibody reduced proliferation and enhanced fluorouracil-induced apoptosis of GC cells. Conclusions: Our findings demonstrate that HOP is an important molecular marker and prognostic factor for GC, and functionally contributes to tumor cell growth and survival. These results provide a rationale for considering HOP as a potential therapeutic target and chemosensitizer in GC.

Original languageEnglish (US)
Pages (from-to)879-892
Number of pages14
JournalCellular Physiology and Biochemistry
Volume47
Issue number2
DOIs
StatePublished - Jun 1 2018

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HSP70 Heat-Shock Proteins
Stomach Neoplasms
Survival
Proteins
Neoplasms
Apoptosis
Cell Survival
Western Blotting
Serum
Cell Proliferation
Messenger RNA
Mitogen-Activated Protein Kinase 3
Caspase 9
Atlases
Mitogen-Activated Protein Kinase 1
B-Cell Lymphoma
Growth
Neutralizing Antibodies
Fluorouracil
Caspase 3

Keywords

  • Apoptosis
  • Autocrine
  • Gastric Cancer
  • Hop
  • Proliferation

ASJC Scopus subject areas

  • Physiology

Cite this

HSP70/HSP90-Organizing Protein Contributes to Gastric Cancer Progression in an Autocrine Fashion and Predicts Poor Survival in Gastric Cancer. / Zhai, Ertao; Liang, Wei; Lin, Yi; Huang, Linlin; He, Xin; Cai, Shirong; Chen, Jianhui; Zhang, Ning; Li, Jiali; Zhang, Qiuyang; He, Yulong; Zeng, Zhirong; Chen, Minhu; Xu, Lixia; Peng, Sui.

In: Cellular Physiology and Biochemistry, Vol. 47, No. 2, 01.06.2018, p. 879-892.

Research output: Contribution to journalArticle

Zhai, E, Liang, W, Lin, Y, Huang, L, He, X, Cai, S, Chen, J, Zhang, N, Li, J, Zhang, Q, He, Y, Zeng, Z, Chen, M, Xu, L & Peng, S 2018, 'HSP70/HSP90-Organizing Protein Contributes to Gastric Cancer Progression in an Autocrine Fashion and Predicts Poor Survival in Gastric Cancer', Cellular Physiology and Biochemistry, vol. 47, no. 2, pp. 879-892. https://doi.org/10.1159/000490080
Zhai, Ertao ; Liang, Wei ; Lin, Yi ; Huang, Linlin ; He, Xin ; Cai, Shirong ; Chen, Jianhui ; Zhang, Ning ; Li, Jiali ; Zhang, Qiuyang ; He, Yulong ; Zeng, Zhirong ; Chen, Minhu ; Xu, Lixia ; Peng, Sui. / HSP70/HSP90-Organizing Protein Contributes to Gastric Cancer Progression in an Autocrine Fashion and Predicts Poor Survival in Gastric Cancer. In: Cellular Physiology and Biochemistry. 2018 ; Vol. 47, No. 2. pp. 879-892.
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AU - Liang, Wei

AU - Lin, Yi

AU - Huang, Linlin

AU - He, Xin

AU - Cai, Shirong

AU - Chen, Jianhui

AU - Zhang, Ning

AU - Li, Jiali

AU - Zhang, Qiuyang

AU - He, Yulong

AU - Zeng, Zhirong

AU - Chen, Minhu

AU - Xu, Lixia

AU - Peng, Sui

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AB - Background/Aims: HSP70/HSP90-organizing protein (HOP) is an adaptor protein that mediates heat shock protein 70 (HSP70) and HSP90 folding. HOP can be secreted by cancer cells and promote malignant cell growth in an autocrine manner. Here, we studied its role in gastric cancer (GC). Methods: HOP mRNA and protein levels were detected by quantitative real-time PCR and western blotting, respectively, and enzyme-linked immunosorbent assay was used to determine the serum levels. Immunohistochemistry was performed to analyze HOP expression in 117 GC tissues and 32 adjacent normal tissues. The Cell Counting Kit-8 cell viability assay, flow cytometry, and western blotting were used to analyze the effects of HOP on cell proliferation and apoptosis, and the potential underlying mechanisms. Results: HOP mRNA and protein levels were significantly higher in GC tissues than in normal tissues in our medical center (P< 0.001) and in The Cancer Genome Atlas database (P< 0.001). GC patients had higher serum levels of HOP than age-matched healthy controls (P< 0.001); however, once tumors were removed, serum levels significantly decreased (P< 0.01). In human GC tissues, increased HOP expression was associated with tumor progression and poor survival. Notably, autocrine HOP promoted cell proliferation through the phospholipase Cγ1-extracellular signal-regulated kinase 1/2-dependent pathway, and inhibited cell apoptosis by regulating the activities of caspase 9, caspase 3, and B-cell lymphoma 2. Blocking extracellular HOP with neutralizing antibody reduced proliferation and enhanced fluorouracil-induced apoptosis of GC cells. Conclusions: Our findings demonstrate that HOP is an important molecular marker and prognostic factor for GC, and functionally contributes to tumor cell growth and survival. These results provide a rationale for considering HOP as a potential therapeutic target and chemosensitizer in GC.

KW - Apoptosis

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KW - Gastric Cancer

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KW - Proliferation

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