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首页> 外文期刊>Cell biology international. >Transcriptional modulation of calcium‐permeable AMPA receptor subunits in glioblastoma by MEK–ERK1/2 inhibitors and their role in invasion
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Transcriptional modulation of calcium‐permeable AMPA receptor subunits in glioblastoma by MEK–ERK1/2 inhibitors and their role in invasion

机译：MEK-ERK1 / 2抑制剂在胶质母细胞瘤中钙可渗透的AMPA受体亚基的转录调节及其在侵袭中的作用

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Abstract Glioblastoma is the most common primary brain tumor. Glioblastoma cells secrete a significant amount of glutamate, which serve as a potential growth factor in glioma pathobiology through their specific receptor subtypes including α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR). Glioblastoma express AMPAR subunits; however, its regulation and activation with downstream intracellular signaling are not well‐understood. Phosphorylated‐extracellular signaling‐regulated kinase (ERK)1/2 is known to regulate the ionotropic glutamate receptors in cortical neurons. The mitogen‐activated protein kinase cascade is frequently activated in several tumors, including glioma. Nonetheless, the association of ERK signaling with AMPAR subunits in glioblastoma is undetermined. Here, we demonstrated potential role of AMPAR in invasion, and the modulation of AMPAR subunits at transcript level by ERK signaling in glioblastoma cells. Inhibition of ERK signaling specifically downregulated the expression of calcium‐permeable AMPAR subunits, GluA1 and GluA4, and upregulated calcium‐impermeable AMPAR subunit GluA2 implying differential regulation of the expression of calcium‐permeable AMPAR subunits of glioblastoma. Concomitantly, it significantly decreased the invasion of U87MG cells. Taken together, these findings suggest that the AMPAR enhances invasion of glioblastoma, and ERK signaling modulates the differential expression of calcium‐permeable AMPAR phenotype that might play a crucial role in the invasive propensity of glioblastoma cells.
机译：胶质母细胞瘤是最常见的原发性脑肿瘤。胶质母细胞瘤细胞分泌大量谷氨酸，通过其特定的受体亚型（包括α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR））在胶质瘤病理生物学中作为潜在的生长因子。胶质母细胞瘤表达AMPAR亚单位；然而，其下游细胞内信号的调节和激活尚不清楚。已知磷酸化细胞外信号调节激酶（ERK）1/2可调节皮质神经元中的离子型谷氨酸受体。丝裂原激活的蛋白激酶级联在包括胶质瘤在内的几种肿瘤中经常被激活。然而，ERK信号与胶质母细胞瘤中AMPAR亚单位的关联尚不确定。在这里，我们证明了AMPAR在侵袭中的潜在作用，以及在胶质母细胞瘤细胞中通过ERK信号在转录水平上调节AMPAR亚基。ERK信号的抑制特异性地下调了钙透性AMPAR亚单位GluA1和GluA4的表达，上调了钙不透性AMPAR亚单位GluA2，这意味着胶质母细胞瘤钙透性AMPAR亚单位表达的差异调节。同时，它显著降低了U87MG细胞的侵袭性。综上所述，这些发现表明AMPAR增强了胶质母细胞瘤的侵袭性，ERK信号调节了钙通透性AMPAR表型的差异表达，这可能在胶质母细胞瘤细胞的侵袭倾向中起到关键作用。

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