Journal article
HB-EGF Activates the EGFR/HIF-1α Pathway to Induce Proliferation of Arsenic-Transformed Cells and Tumor Growth
Frontiers in oncology, Vol.10, pp.1019-1019
06/30/2020
DOI: 10.3389/fonc.2020.01019
PMID: 32695675
Abstract
Arsenic was recently identified as a pollutant that is a major cause of lung cancer. Since heparin-binding EGF-like growth factor (HB-EGF) was reported to be a promising therapeutic target for lung cancer, we investigated the role and mechanism of HB-EGF during arsenic-induced carcinogenesis and development of lung cancer. HB-EGF expression were upregulated in As-T cells, lung cancer cell lines, and in most lung cancer tissue samples; and HB-EGF activated the EGFR/p-ERK/HIF-1α pathway and induced VEGF by regulating HIF-1α transcription. HIF-1α transcriptional stimulation by HB-EGF was facilitated by PKM2 and played an important role in HB-EGF's effect on cells. An HB-EGF inhibitor(CRM197, cross-reacting material 197) slowed cell proliferation and inhibited migration of As-T and A549 cells, and inhibited tumor growth. PKM2 also played an important role in the proliferation and migration in As-T cells. The positive staining ratios of EGFR phosphorylation (Y1068) and PKM2 were significantly higher in most cases of lung cancer than in paired normal tumor-adjacent lung tissues; and HB-EGF expression levels strongly correlated with p-EGFR expression levels. Thus, HB-EGF drives arsenic-induced carcinogenesis, tumor growth, and lung cancer development via the EGFR/PKM2/HIF-1α pathway.
Details
- Title: Subtitle
- HB-EGF Activates the EGFR/HIF-1α Pathway to Induce Proliferation of Arsenic-Transformed Cells and Tumor Growth
- Creators
- Lin Wang - Department of Pathology, Nanjing Medical UniversityYi-Fan Lu - Department of Pathology, Nanjing Medical UniversityChao-Shan Wang - Department of Pathology, Nanjing Medical UniversityYun-Xia Xie - The Academy of Medical Sciences, Zhengzhou UniversityYan-Qiu Zhao - Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou UniversityYing-Chen Qian - Department of Pathology, Nanjing Medical UniversityWei-Tao Liu - Department of Pathology, Nanjing Medical UniversityMin Wang - Department of Pathology, Nanjing Medical UniversityBing-Hua Jiang - Department of Pathology, The University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in oncology, Vol.10, pp.1019-1019
- DOI
- 10.3389/fonc.2020.01019
- PMID
- 32695675
- NLM abbreviation
- Front Oncol
- ISSN
- 2234-943X
- eISSN
- 2234-943X
- Publisher
- Frontiers Media S.A
- Language
- English
- Date published
- 06/30/2020
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984066106602771
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