基于PyMQ構(gòu)建的PKM2蛋白結(jié)構(gòu)，圖片來自維基共享資源,。
根據(jù)2012年1月23日在線發(fā)表在Journal of Experimental Medicine期刊上的一項(xiàng)研究,，當(dāng)氧氣稀缺時(shí),，破壞一種允許癌細(xì)胞生長的蛋白能夠?qū)е履[瘤退化。
在癌細(xì)胞中,，一種稱作PKM2(丙酮酸激酶M2異構(gòu)體)的酶大量產(chǎn)生,，從而允許它們?cè)谀[瘤內(nèi)部發(fā)現(xiàn)的嚴(yán)峻低氧環(huán)境中產(chǎn)生能量。
美國麻省理工學(xué)院的Michael Goldberg和Phillip Sharp如今發(fā)現(xiàn)抑制PKM2能夠剝奪癌細(xì)胞的能量從而殺死它們,，但是讓正常細(xì)胞毫發(fā)無損,。破壞PKM2導(dǎo)致小鼠中建立的腫瘤消失。如果這些結(jié)果在人類中仍然正確的話,，這種策略可能提供一種有效的對(duì)抗很多種癌癥類型的方法,，同時(shí)使得產(chǎn)生的副作用最小化。(生物谷：towersimper編譯)
doi:10.1084/jem.20111487
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Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression
Michael S. Goldberg and Phillip A. Sharp
The development of cancer-specific therapeutics has been limited because most healthy cells and cancer cells depend on common pathways. Pyruvate kinase (PK) exists in M1 (PKM1) and M2 (PKM2) isoforms. PKM2, whose expression in cancer cells results in aerobic glycolysis and is suggested to bestow a selective growth advantage, is a promising target. Because many oncogenes impart a common alteration in cell metabolism, inhibition of the M2 isoform might be of broad applicability. We show that several small interfering (si) RNAs designed to target mismatches between the M2 and M1 isoforms confer specific knockdown of the former, resulting in decreased viability and increased apoptosis in multiple cancer cell lines but less so in normal fibroblasts or endothelial cells. In vivo delivery of siPKM2 additionally causes substantial tumor regression of established xenografts. Our results suggest that the inherent nucleotide-level specificity of siRNA can be harnessed to develop therapeutics that target isoform-specific exons in genes exhibiting differential splicing patterns in various cell types.
