{"doi":"10.3389/fonc.2020.01019","title":"HB-EGF Activates the EGFR/HIF-1α Pathway to Induce Proliferation of Arsenic-Transformed Cells and Tumor Growth","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.","journal":"Frontiers in Oncology","year":2020,"id":75704,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":395277,"name":"Yifan Lu","orcid":"0009-0009-4158-9345","position":1,"is_corresponding":false},{"id":396394,"name":"Chaoshan Wang","orcid":null,"position":2,"is_corresponding":false},{"id":396395,"name":"Yun-Xia Xie","orcid":null,"position":3,"is_corresponding":false},{"id":395278,"name":"Yanqiu Zhao","orcid":"0000-0001-7925-3606","position":4,"is_corresponding":false},{"id":395279,"name":"Ying-Chen Qian","orcid":"0000-0001-5928-4456","position":5,"is_corresponding":false},{"id":395280,"name":"Weitao Liu","orcid":"0000-0002-0954-9943","position":6,"is_corresponding":false},{"id":395281,"name":"Min Wang","orcid":"0009-0004-6321-2980","position":7,"is_corresponding":false},{"id":49478,"name":"Bing‐Hua Jiang","orcid":"0000-0003-4526-2031","position":8,"is_corresponding":false},{"id":264446,"name":"Lin Wang","orcid":"0000-0001-5716-6587","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T21:46:55.856612Z","pmid":"32695675","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}