Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as...Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.展开更多
BACKGROUND： Conventional neuroimaging diagnosis does not assist with the monitoring or evaluation of basal nuclei ischemic and hemorrhagic stroke, or motor functional recovery. Magnetic resonance, diffusion tensor im...BACKGROUND： Conventional neuroimaging diagnosis does not assist with the monitoring or evaluation of basal nuclei ischemic and hemorrhagic stroke, or motor functional recovery. Magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography have all been used to observe features of cerebral white matter fibrous structures. In addition, diffusion tensor tractography is the only non-invasive imaging method to display the corticospinal tract in vivo. OBJECTIVE： To evaluate the impairment degree of corticospinal tract induced by basal nuclei ischemic and hemorrhagic stroke through the use of magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography, and to analyze the correlation to muscular strength. DESIGN, TIME AND SETTING： A retrospective case analysis was performed at the Department of Medical Imaging, Neurology and Neurosurgery, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA between November 2002 and June 2008. PARTICIPANTS： A total of 15 patients with acute or subacute cerebral ischemic stroke and nine with hemorrhagic stroke in the basal nuclei were selected. METHODS： Magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography results and data were analyzed. Fractional anisotropy and directionally encoded color maps were obtained. Three-dimensional tractography of bilateral corticospinal tract was created, and corticospinal tract integrity was graded. Fractional anisotropy of infarct region and corresponding contralateral normal regions were measured, and hematoma volume in hemorrhagic stroke patients was determined. Hand motor function ability was evaluated using Brunstorm criteria. MAIN OUTCOME MEASURES： Fractional anisotropy of infarct region and corresponding contralateral normal regions; hematoma volume in hemorrhagic stroke patients; correlation between muscular strength and corticospinal tract impairment degree in ischemic stroke and hemorrhagic stroke patients before and after treatment. RESULTS： In ischemic stroke patients, the fractional anisotropy value was significantly lower in the infarct area of white matter than in the normal hemisphere （P 〈 0.01）. The impairment degree of corticospinal tract negatively correlated with muscular strength of the corresponding hand （r = -0.97 P 〈 0.01）. The hematoma volume of hemorrhagic stroke patients significantly negatively correlated with Spearman test results for muscular strength of the corresponding hand （r = -0.88, P 〈 0.01）. CONCLUSION： Corticospinal tract impairment severity negatively correlated with muscular strength and motor functional recovery, which suggested that diffusion tensor imaging and diffusion tensor tractography could be used to evaluate corticospinal tract motor function.展开更多
基金supported by grants from the National Natural Science Foundation of China(82204428,U24A20815,82304526,82204427,82201001,82430108,82293681(82293680),82273941)the National High-level Personnelof Special Support Program(to Dongmei Zhang and Minfeng Chen)+5 种基金the Natural Science Foundation of Guangdong Province(2023A1515010361 and 2022A1515011813)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020098)the Science and Technology Program of Guangzhou(SL2024A04J00410,SL2024A04J00374,SL2024A04J00280)the Fundamental Research Funds for The Central Universities(21624103)the Science and Technology Projects in Guangzhou(2023A03J1030,202201010173,202102070001)the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(JNU1AF-CFTP-2022-a01210).
文摘Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.
基金a Grant from the Science and Technology Department of Fujian Province,No.2006J0192
文摘BACKGROUND： Conventional neuroimaging diagnosis does not assist with the monitoring or evaluation of basal nuclei ischemic and hemorrhagic stroke, or motor functional recovery. Magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography have all been used to observe features of cerebral white matter fibrous structures. In addition, diffusion tensor tractography is the only non-invasive imaging method to display the corticospinal tract in vivo. OBJECTIVE： To evaluate the impairment degree of corticospinal tract induced by basal nuclei ischemic and hemorrhagic stroke through the use of magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography, and to analyze the correlation to muscular strength. DESIGN, TIME AND SETTING： A retrospective case analysis was performed at the Department of Medical Imaging, Neurology and Neurosurgery, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA between November 2002 and June 2008. PARTICIPANTS： A total of 15 patients with acute or subacute cerebral ischemic stroke and nine with hemorrhagic stroke in the basal nuclei were selected. METHODS： Magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography results and data were analyzed. Fractional anisotropy and directionally encoded color maps were obtained. Three-dimensional tractography of bilateral corticospinal tract was created, and corticospinal tract integrity was graded. Fractional anisotropy of infarct region and corresponding contralateral normal regions were measured, and hematoma volume in hemorrhagic stroke patients was determined. Hand motor function ability was evaluated using Brunstorm criteria. MAIN OUTCOME MEASURES： Fractional anisotropy of infarct region and corresponding contralateral normal regions; hematoma volume in hemorrhagic stroke patients; correlation between muscular strength and corticospinal tract impairment degree in ischemic stroke and hemorrhagic stroke patients before and after treatment. RESULTS： In ischemic stroke patients, the fractional anisotropy value was significantly lower in the infarct area of white matter than in the normal hemisphere （P 〈 0.01）. The impairment degree of corticospinal tract negatively correlated with muscular strength of the corresponding hand （r = -0.97 P 〈 0.01）. The hematoma volume of hemorrhagic stroke patients significantly negatively correlated with Spearman test results for muscular strength of the corresponding hand （r = -0.88, P 〈 0.01）. CONCLUSION： Corticospinal tract impairment severity negatively correlated with muscular strength and motor functional recovery, which suggested that diffusion tensor imaging and diffusion tensor tractography could be used to evaluate corticospinal tract motor function.
