ArticleScientific reports2019
HER2/HER3 regulates lactate secretion and expression of lactate receptor mRNA through the MAP3K4 associated protein GIT1.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Spatiotemporal heterogeneity of neutrophil extracellular traps in hepatocellular carcinoma microenvironment and targeted therapy progress.Journal of translational medicine · 2026Review
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- Microbiome-driven resistance in cervical cancer therapy: from mechanistic dissection to clinical translation.Expert reviews in molecular medicine · 2025Review
- MAP3K4 kinase action and dual role in cancer.Discover oncology · 2024Review
- Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.Cancer cell · 2023Article
- Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
One of the major features of cancer is Otto Warburg's observation that many tumors have increased extracellular acidification compared to healthy tissues. Since Warburg's observation, the importance of extracellular acidification in cancer is now considered a hallmark of cancer. Human MAP3K4 functions upstream of the p38 and JNK mitogen activated protein kinases (MAPKs). Additionally, MAP3K4 is required for cell migration and extracellular acidification of breast cancer cells in response to HER2/HER3 signaling. Here, we demonstrate that GIT1 interacts with MAP3K4 by immunoprecipitation, while cellular lactate production and the capacity of MCF-7 cells for anchorage independent growth in soft agar were dependent on GIT1. Additionally, we show that activation of HER2/HER3 signaling leads to reduced expression of lactate receptor (GPR81) mRNA and that both, GIT1 and MAP3K4, are necessary for constitutive expression of GPR81 mRNA. Our study suggests that targeting downstream proteins in the HER2/HER3-induced extracellular lactate signaling pathway may be a way to inhibit the Warburg Effect to disrupt tumor growth.
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Registered trials
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