ArticleCellular signalling2014
HER2/HER3 regulates extracellular acidification and cell migration through MTK1 (MEKK4).
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- Investigating the role of EGFR signalling in muscle dystrophies: implications for Duchenne muscular dystrophy.Cell death & disease · 2026Article
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4.Cell communication and signaling : CCS · 2024Article
- MAP3K4 kinase action and dual role in cancer.Discover oncology · 2024Review
- Construction of a Matrix Cancer-Associated Fibroblast Signature Gene-Based Risk Prognostic Signature for Directing Immunotherapy in Patients with Breast Cancer Using Single-Cell Analysis and Machine Learning.International journal of molecular sciences · 2023Article
- Upregulation of lncRNA GATA6-AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK-1.Oncology letters · 2019Article
- HER2/HER3 regulates lactate secretion and expression of lactate receptor mRNA through the MAP3K4 associated protein GIT1.Scientific reports · 2019Article
- Article
- Long non-coding RNA-OIS1 inhibits HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MTK-1.Oncology letters · 2019Article
- Downregulation of ERBB3 decreases the proliferation, migration and invasion of cervical cancer cells though the interaction with MTK-1.Oncology letters · 2018Article
- BMP2 rescues deficient cell migration in Tgfbr3(-/-) epicardial cells and requires Src kinase.Cell adhesion & migration · 2016Article
- Arsenite Disrupts Zinc-Dependent TGFβ2-SMAD Activity During Murine Cardiac Progenitor Cell Differentiation.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Article
- Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells.Molecular and cellular biology · 2015Article
- Article
- Cardiac epithelial-mesenchymal transition is blocked by monomethylarsonous acid (III).Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human MAP3K4 (MTK1) functions upstream of mitogen activated protein kinases (MAPKs). In this study we show MTK1 is required for human epidermal growth factor receptor 2/3 (HER2/HER3)-heregulin beta1 (HRG) induced cell migration in MCF-7 breast cancer cells. We demonstrate that HRG stimulation leads to association of MTK1 with activated HER3 in MCF-7 and T-47D breast cancer cells. Activated HER3 association with MTK1 is dependent on HER2 activation and is decreased by pre-treatment with the HER2 inhibitor, lapatinib. Moreover, we also identify the actin interacting region (AIR) on MTK1. Disruption of actin cytoskeletal polymerization with cytochalasin D inhibited HRG induced MTK1/HER3 association. Additionally, HRG stimulation leads to extracellular acidification that is independent of cellular proliferation. HRG induced extracellular acidification is significantly inhibited when MTK1 is knocked down in MCF-7 cells. Similarly, pre-treatment with lapatinib significantly decreased HRG induced extracellular acidification. Extracellular acidification is linked with cancer cell migration. We performed scratch assays that show HRG induced cell migration in MCF-7 cells. Knockdown of MTK1 significantly inhibited HRG induced cell migration. Furthermore, pre-treatment with lapatinib also significantly decreased cell migration. Cell migration is required for cancer cell metastasis, which is the major cause of cancer patient mortality. We identify MTK1 in the HER2/HER3-HRG mediated extracellular acidification and cell migration pathway in breast cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.