ArticleInternational journal of molecular sciences2018
Lactate Transporter Monocarboxylate Transporter 4 Induces Bone Pain in Head and Neck Squamous Cell Carcinoma.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The trial behind it
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
9 citing papers in PubMed, 10 citations in OpenAlex.
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- MCT4 deficiency suppresses tumor incidence and metastasis by downregulating IGF1 expression and enhancing anti-tumor immunity.Communications biology · 2026Article
- Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies.Military Medical Research · 2025Review
- Pain, lactate, and anesthetics: intertwined regulators of tumor metabolism and immunity.Frontiers in oncology · 2025Review
- Lactate secreted via MCT4 from bone‑colonizing breast cancer excites sensory neurons via GPR81.International journal of oncology · 2023Article
- The HMGB1/RAGE axis induces bone pain associated with colonization of 4T1 mouse breast cancer in bone.Journal of bone oncology · 2021Article
- High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer.Oncology reports · 2020Article
- Effects of Lactate on One Class of Group III (CT3) Muscle Afferents.Frontiers in cellular neuroscience · 2020Article
- Inhibition Of Monocarboxylate Transporter 1 In Spinal Cord Horn Significantly Reverses Chronic Inflammatory Pain.Journal of pain research · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically, as it can invade facial bones and cause bone pain that is undertreated and poorly understood. Here we studied HNSCC bone pain (HNSCC-BP) in an intratibial mouse xenograft model that uses a human HNSCC cell line (SAS cells). These mice develop HNSCC-BP associated with an upregulation of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in the dorsal root ganglia (DRGs) of sensory nerve cell bodies. Our experiments demonstrated that the inhibition of monocarboxylate transporter 4 (MCT4) by short hairpin (shRNA) transduction suppressed the HNSCC-BP, the lactate level in bone marrow, and the pERK1/2 expression in DRG. The sensory nerves also expressed increased levels of the acid-sensing receptor TRPV1. DRG neurons co-cultured with SAS cells showed increased neurite outgrowth, and were inhibited by MCT4 silencing with shRNA. Collectively, our results show that HNSCC induced an acidic bone microenvironment that evokes HNSCC-BP via MCT4 expression.
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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.