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Molecular Cancer文章:揭示胃癌和糖代谢酶FBP2的关系

据报道,癌症也是一种代谢疾病。为了研究胃癌和糖代谢相关基因的功能关系,研究人员对FBP2基因进行了一系列体外实验和甲基化研究,相关成果发表在2013年第12卷的《Molecular Cancer》上。作者通过前期芯片研究发现和癌旁组织相比,胃癌样品中和葡萄糖代谢途径相关的果糖-1,6-二磷酸FBP2基因表达量显著降低,且该基因的表达量降低和胃癌患者拥有较差的存活率相关联 (P = 0.019)。FBP2基因编码的蛋白是一种可以将果糖-1,6-二磷酸催化成为果糖-6-磷酸和无机磷酸盐的代谢酶。作者通过体外实验,在胃癌细胞中异位表达FBP2可以激活AMPK信号途径,通过抑制Akt-mTOR途径抑制葡萄糖代谢,从而增加了细胞凋亡,减小了细胞的增殖。进一步通过Sequenom甲基化研究发现FBP2基因启动子区甲基化程度增加,且用去甲基化试剂5-Aza处理胃癌细胞后导致该基因表达量升高。在裸鼠模型中异位表达FBP2基因,消除了胃癌细胞的肿瘤形成。这些研究结果表明FBP2基因表达情况可以作为胃癌患者靶向治疗的潜在策略。本研究甲基化(Sequenom 甲基化)实验博奥生物集团有限公司完成。


原文摘要:Decreased fructose-1,6-bisphosphatase-2 expression promotes glycolysis and growth in gastric cancer cells

Abstract
Background: Increasing evidence suggests that cancer is a metabolic disease. Here, we investigated the potential role of fructose-1,6-bisphosphatase-2 (FBP2), the enzyme that catalyses the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate in glucose metabolism, in gastric cancer (GC) development.
Results: Our data indicated that FBP2 was downregulated in GC tissues (86.2%, 100/116), and absent or low FBP2 expression in GC tissues was correlated with poor survival of GC patients (P = 0.019). Conversely, ectopic expression of FBP2 in GC cells activated AMP-activated protein kinase (AMPK) signalling, inhibited the Akt-mTOR pathway, suppressed glucose metabolism, enhanced apoptosis, and reduced cell proliferation. Bisulphite genomic sequencing (BGS) in gastric cancer cell lines revealed that the FBP2 promoter region was densely methylated, and
treatment of GC cells with the demethylation reagent, 5-aza-2-deoxycytidine (5-Aza), led to an increase in FBP2 expression. Importantly, forced expression of FBP2 abrogated tumour formation of these GC cells in nude mice.

Conclusion: Our results indicate that FBP2 does negatively regulate cell growth, and reduced expression of FBP2 may contribute to carcinogenesis for GC. These findings suggest that restoration of FBP2 expression can be a promising strategy for the target therapy of GC.

原文出处:http://www.biomedcentral.com/content/pdf/1476-4598-12-110.pdf