ArticleJournal of molecular medicine (Berlin, Germany)2014
ErbB targeting inhibitors repress cell migration of esophageal squamous cell carcinoma and adenocarcinoma cells by distinct signaling pathways.
Article in Journal of molecular medicine (Berlin, Germany), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
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- Gα13 Contributes to LPS-Induced Morphological Alterations and Affects Migration of Microglia.Molecular neurobiology · 2021Article
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- Downregulation of miR-375 contributes to ERBB2-mediated VEGFA overexpression in esophageal cancer.Journal of Cancer · 2021Article
- HER2 expression and relevant clinicopathological features in esophageal squamous cell carcinoma in a Chinese population.Diagnostic pathology · 2020Article
- Time series expression pattern of key genes reveals the molecular process of esophageal cancer.Bioscience reports · 2020Article
- Cryptotanshinone inhibits esophageal squamous-cell carcinoma in vitro and in vivo through the suppression of STAT3 activation.OncoTargets and therapy · 2019Article
- Combination of Selected MET and EGFR Inhibitors Decreases Melanoma Cells' Invasive Abilities.Frontiers in pharmacology · 2019Article
- High Content Screening Characterization of Head and Neck Squamous Cell Carcinoma Multicellular Tumor Spheroid Cultures Generated in 384-Well Ultra-Low Attachment Plates to Screen for Better Cancer Drug Leads.Assay and drug development technologies · 2019Article
- Maftools: efficient and comprehensive analysis of somatic variants in cancer.Genome research · 2018Article
- Development of Normal and Cleft Palate: A Central Role for Connective Tissue Growth Factor (CTGF)/CCN2.Journal of developmental biology · 2018Review
- A new model system identifies epidermal growth factor receptor-human epidermal growth factor receptor 2 (HER2) and HER2-human epidermal growth factor receptor 3 heterodimers as potent inducers of oesophageal epithelial cell invasion.The Journal of pathology · 2017Article
- The production of 3D tumor spheroids for cancer drug discovery.Drug discovery today. Technologies · 2017Review
- Targeted delivery of an ADP-ribosylating bacterial toxin into cancer cells.Scientific reports · 2017Article
- Resveratrol mediates cell cycle arrest and cell death in human esophageal squamous cell carcinoma by directly targeting the EGFR signaling pathway.Oncology letters · 2017Article
- Subcellular localization of EGFR in esophageal carcinoma cell lines.Journal of cell communication and signaling · 2016Article
- RND1 is up-regulated in esophageal squamous cell carcinoma and promotes the growth and migration of cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Model-based assessment of erlotinib effect in vitro measured by real-time cell analysis.Journal of pharmacokinetics and pharmacodynamics · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledErbB family receptor tyrosine kinases (ErbBs) play a role in cell adhesion and migration and are frequently overexpressed in esophageal squamous cell carcinomas (ESCCs) or esophageal adenocarcinomas (EACs). Targeting ErbBs by tyrosine kinase inhibitors (TKIs) may therefore limit esophageal cancer cell migration. Here, we studied the impact of TKIs on ErbB dimerization, cell signaling pathways, and cell migration in three esophageal cell lines: OE21 (ESCC), OE33 (EAC), and Het-1A (non-neoplastic esophageal epithelium). In OE21 cells, the TKIs erlotinib, gefitinib, and lapatinib slightly affected epidermal growth factor receptor EGFR/EGFR, but not EGFR/HER2 dimerization as detected by in situ proximity ligation assay (in situ PLA). Still, TKIs inhibited ERK1/2, Akt, STAT3, and RhoA activity in OE21 cells, as assessed by Western blot, antibody arrays, and Rho GTPase effector pull-down assays. This was accompanied by reduced OE21 cell migration, induction of focal adhesions, and actin cytoskeleton reorganization, as shown by Oris™ migration assay and focal adhesion kinase (FAK)/phalloidin staining. In contrast, in OE33 cells, only lapatinib decreased STAT5, Src family kinase (SFK), and FAK activity as well as β-catenin expression. This impeded cell migration and induced morphological changes in OE33 cells. No alterations were seen for the non-neoplastic Het-1A cells. Thus, we identified the ErbB signaling network as regulator of esophageal cancer cell's actin cytoskeleton, focal adhesions, and cell migration. ErbB targeted TKIs therefore also limit ESCC and EAC cell motility and migration. KEY MESSAGE: Clinical tyrosine kinase inhibitors (TKIs) reduce esophageal cancer cell migration. Loss of cell migration is linked to reduced Akt, ERK1/2, STAT (3 or 5), FAK, SFKs, and RhoA activity. Clinical TKIs act via distinct signaling in the two main histotypes of esophageal cancer.
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