Lysine-specific demethylase-1 contributes to malignant behavior by regulation of invasive activity and metabolic shift in esophageal cancer
Lysine-specific demethylase-1 contributes to malignant behavior by regulation of invasive activity and metabolic shift in esophageal cancer
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DOI：
10.1002/ijc.29714
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发表时间：
2016-01-15
影响因子：
6.4
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
--
作者：
Kosumi, Keisuke;Baba, Yoshifumi;Baba, Hideo
赖氨酸特异性去甲基化酶 1 (LSD1) 可去除组蛋白 H3 的单甲基化和二甲基化赖氨酸 4 上的甲基。先前的研究已将LSD1与多种人类肿瘤的恶性肿瘤联系起来，并且LSD1被认为对脂肪细胞和肝细胞癌中的能量代谢基因进行表观遗传调节。本研究探讨LSD1在食管癌细胞侵袭活性和代谢中的功能。我们研究了LSD1免疫组织化学表达水平是否与临床和病理特征相关，包括氟脱氧葡萄糖正电子发射断层扫描测定中的最大标准摄取值。通过使用 LSD1 特异性小干扰 RNA 和 LSD1 抑制剂，在体外评估 LSD1 对细胞增殖、侵袭和葡萄糖摄取的影响。我们还通过细胞外通量分析仪测量细胞外酸化率（ECAR）和耗氧率（OCR）来评估两种主要的能量途径（糖酵解途径和线粒体呼吸）。 LSD1免疫组化高表达与食管癌患者的高肿瘤分期、淋巴管侵犯、不良预后和高最大标准摄取值显着相关。在体外分析中，LSD1敲低显着抑制癌细胞的侵袭活性和葡萄糖摄取，降低其ECAR并增加其OCR和OCR/ECAR。 LSD1可能通过调节食管癌细胞的侵袭活性和代谢、激活糖酵解途径和抑制线粒体呼吸而导致恶性行为。结果支持 LSD1 作为潜在的治疗靶点。
Lysine-specific demethylase-1 (LSD1) removes the methyl groups from mono-and di-methylated lysine 4 of histone H3. Previous studies have linked LSD1 to malignancy in several human tumors, and LSD1 is considered to epigenetically regulate the energy metabolism genes in adipocytes and hepatocellular carcinoma. This study investigates the function of LSD1 in the invasive activity and the metabolism of esophageal cancer cells. We investigated whether LSD1 immunohistochemical expression levels are related to clinical and pathological features, including the maximum standard uptake value in fluorodeoxyglucose positron emission tomography assay. The influence of LSD1 on cell proliferation, invasion and glucose uptake was evaluated in vitro by using specific small interfering RNA for LSD1, and an LSD1 inhibitor. We also evaluated two major energy pathways (glycolytic pathway and mitochondrial respiration) by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) with an extracellular flux analyzer. High LSD1 immunohistochemical expression was significantly associated with high tumor stage, lymphovascular invasion, poor prognosis, and high maximum standard uptake value in esophageal cancer patients. In the in vitro analysis, LSD1 knockdown significantly suppressed the invasive activity and glucose uptake of cancerous cells, reduced their ECAR and increased their OCR and OCR/ECAR. LSD1 may contribute to malignant behavior by regulating the invasive activity and metabolism, activating the glycolytic pathway and inhibiting the mitochondrial respiration of esophageal cancer cells. The results support LSD1 as a potential therapeutic target.