Oct4 upregulates osteopontin via Egr1 and is associated with poor outcome in human lung cancer

Yin Hsun Feng, Yu Chu Su, Shuo Fu Lin, Pey Ru Lin, Chao-Liang Wu, Chao Ling Tung, Chien Feng Li, Gia Shing Shieh, Ai-Li Shiau

Research output: Contribution to journalArticle

Abstract

Background: Roles of cancer stem cells and early growth response gene 1 (Egr1) in carcinogenesis have been extensively studied in lung cancer. However, the role of Egr1 in the metastasis of lung cancer remains undetermined, especially in regard to stem cell-related pathways. Methods: Egr1, osteopontin (OPN) and Oct4 expression in human lung cancer was determined by performing immunohistochemistry. Immunoblotting, ELISA, luciferase reporter assay, chromatin immunoprecipitation assay and RT-PCR were performed to validate the regulation of Oct4-Egr1-OPN axis. Moreover, the effect of Oct4-Egr1-OPN axis on lung cancer progression was evaluated by cell migration assay and mice study. Results: We detected Oct4, Egr1, and OPN expression in clinical specimens from 79 lung cancer patients, including 72 adenocarcinomas and 7 squamous cell carcinomas. High expression of Oct4, Egr1, and OPN accounted for 53, 51, and 57% of the patients, respectively. All of the three biomarkers were positively correlated in clinical human lung cancer. Patients with high expression of OPN were significantly associated with shorter disease-free survivals than those with low expression of OPN (p < 0.05). In lung cancer cells, Oct4 transactivated the Egr1 promoter and upregulated Egr1 expression. In a human lung cancer xenograft model, Oct4-overexpressing tumors expressed elevated levels of Egr1. Furthermore, overexpression of Oct4 in lung cancer cells increased the metastatic potential. Conclusions: Egr1 exerts a promoting effect on cancer metastasis in Oct4-overexpressing lung cancer. Thus, therapeutic strategies targeting the Oct4/Egr1/OPN axis may be further explored for the treatment of lung cancer, especially when lung cancer is refractory to conventional treatment due to cancer stem cells.

Original languageEnglish
Article number791
JournalBMC cancer
Volume19
Issue number1
DOIs
Publication statusPublished - 2019 Aug 9

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Osteopontin
Lung Neoplasms
Up-Regulation
Growth
Genes
Neoplastic Stem Cells
Cell Migration Assays
Neoplasm Metastasis
Chromatin Immunoprecipitation
Luciferases
Immunoblotting
Heterografts
Disease-Free Survival
Squamous Cell Carcinoma
Neoplasms
Carcinogenesis
Adenocarcinoma
Stem Cells
Therapeutics
Biomarkers

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

Cite this

Feng, Yin Hsun ; Su, Yu Chu ; Lin, Shuo Fu ; Lin, Pey Ru ; Wu, Chao-Liang ; Tung, Chao Ling ; Li, Chien Feng ; Shieh, Gia Shing ; Shiau, Ai-Li. / Oct4 upregulates osteopontin via Egr1 and is associated with poor outcome in human lung cancer. In: BMC cancer. 2019 ; Vol. 19, No. 1.
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title = "Oct4 upregulates osteopontin via Egr1 and is associated with poor outcome in human lung cancer",
abstract = "Background: Roles of cancer stem cells and early growth response gene 1 (Egr1) in carcinogenesis have been extensively studied in lung cancer. However, the role of Egr1 in the metastasis of lung cancer remains undetermined, especially in regard to stem cell-related pathways. Methods: Egr1, osteopontin (OPN) and Oct4 expression in human lung cancer was determined by performing immunohistochemistry. Immunoblotting, ELISA, luciferase reporter assay, chromatin immunoprecipitation assay and RT-PCR were performed to validate the regulation of Oct4-Egr1-OPN axis. Moreover, the effect of Oct4-Egr1-OPN axis on lung cancer progression was evaluated by cell migration assay and mice study. Results: We detected Oct4, Egr1, and OPN expression in clinical specimens from 79 lung cancer patients, including 72 adenocarcinomas and 7 squamous cell carcinomas. High expression of Oct4, Egr1, and OPN accounted for 53, 51, and 57{\%} of the patients, respectively. All of the three biomarkers were positively correlated in clinical human lung cancer. Patients with high expression of OPN were significantly associated with shorter disease-free survivals than those with low expression of OPN (p < 0.05). In lung cancer cells, Oct4 transactivated the Egr1 promoter and upregulated Egr1 expression. In a human lung cancer xenograft model, Oct4-overexpressing tumors expressed elevated levels of Egr1. Furthermore, overexpression of Oct4 in lung cancer cells increased the metastatic potential. Conclusions: Egr1 exerts a promoting effect on cancer metastasis in Oct4-overexpressing lung cancer. Thus, therapeutic strategies targeting the Oct4/Egr1/OPN axis may be further explored for the treatment of lung cancer, especially when lung cancer is refractory to conventional treatment due to cancer stem cells.",
author = "Feng, {Yin Hsun} and Su, {Yu Chu} and Lin, {Shuo Fu} and Lin, {Pey Ru} and Chao-Liang Wu and Tung, {Chao Ling} and Li, {Chien Feng} and Shieh, {Gia Shing} and Ai-Li Shiau",
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Oct4 upregulates osteopontin via Egr1 and is associated with poor outcome in human lung cancer. / Feng, Yin Hsun; Su, Yu Chu; Lin, Shuo Fu; Lin, Pey Ru; Wu, Chao-Liang; Tung, Chao Ling; Li, Chien Feng; Shieh, Gia Shing; Shiau, Ai-Li.

In: BMC cancer, Vol. 19, No. 1, 791, 09.08.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oct4 upregulates osteopontin via Egr1 and is associated with poor outcome in human lung cancer

AU - Feng, Yin Hsun

AU - Su, Yu Chu

AU - Lin, Shuo Fu

AU - Lin, Pey Ru

AU - Wu, Chao-Liang

AU - Tung, Chao Ling

AU - Li, Chien Feng

AU - Shieh, Gia Shing

AU - Shiau, Ai-Li

PY - 2019/8/9

Y1 - 2019/8/9

N2 - Background: Roles of cancer stem cells and early growth response gene 1 (Egr1) in carcinogenesis have been extensively studied in lung cancer. However, the role of Egr1 in the metastasis of lung cancer remains undetermined, especially in regard to stem cell-related pathways. Methods: Egr1, osteopontin (OPN) and Oct4 expression in human lung cancer was determined by performing immunohistochemistry. Immunoblotting, ELISA, luciferase reporter assay, chromatin immunoprecipitation assay and RT-PCR were performed to validate the regulation of Oct4-Egr1-OPN axis. Moreover, the effect of Oct4-Egr1-OPN axis on lung cancer progression was evaluated by cell migration assay and mice study. Results: We detected Oct4, Egr1, and OPN expression in clinical specimens from 79 lung cancer patients, including 72 adenocarcinomas and 7 squamous cell carcinomas. High expression of Oct4, Egr1, and OPN accounted for 53, 51, and 57% of the patients, respectively. All of the three biomarkers were positively correlated in clinical human lung cancer. Patients with high expression of OPN were significantly associated with shorter disease-free survivals than those with low expression of OPN (p < 0.05). In lung cancer cells, Oct4 transactivated the Egr1 promoter and upregulated Egr1 expression. In a human lung cancer xenograft model, Oct4-overexpressing tumors expressed elevated levels of Egr1. Furthermore, overexpression of Oct4 in lung cancer cells increased the metastatic potential. Conclusions: Egr1 exerts a promoting effect on cancer metastasis in Oct4-overexpressing lung cancer. Thus, therapeutic strategies targeting the Oct4/Egr1/OPN axis may be further explored for the treatment of lung cancer, especially when lung cancer is refractory to conventional treatment due to cancer stem cells.

AB - Background: Roles of cancer stem cells and early growth response gene 1 (Egr1) in carcinogenesis have been extensively studied in lung cancer. However, the role of Egr1 in the metastasis of lung cancer remains undetermined, especially in regard to stem cell-related pathways. Methods: Egr1, osteopontin (OPN) and Oct4 expression in human lung cancer was determined by performing immunohistochemistry. Immunoblotting, ELISA, luciferase reporter assay, chromatin immunoprecipitation assay and RT-PCR were performed to validate the regulation of Oct4-Egr1-OPN axis. Moreover, the effect of Oct4-Egr1-OPN axis on lung cancer progression was evaluated by cell migration assay and mice study. Results: We detected Oct4, Egr1, and OPN expression in clinical specimens from 79 lung cancer patients, including 72 adenocarcinomas and 7 squamous cell carcinomas. High expression of Oct4, Egr1, and OPN accounted for 53, 51, and 57% of the patients, respectively. All of the three biomarkers were positively correlated in clinical human lung cancer. Patients with high expression of OPN were significantly associated with shorter disease-free survivals than those with low expression of OPN (p < 0.05). In lung cancer cells, Oct4 transactivated the Egr1 promoter and upregulated Egr1 expression. In a human lung cancer xenograft model, Oct4-overexpressing tumors expressed elevated levels of Egr1. Furthermore, overexpression of Oct4 in lung cancer cells increased the metastatic potential. Conclusions: Egr1 exerts a promoting effect on cancer metastasis in Oct4-overexpressing lung cancer. Thus, therapeutic strategies targeting the Oct4/Egr1/OPN axis may be further explored for the treatment of lung cancer, especially when lung cancer is refractory to conventional treatment due to cancer stem cells.

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