新加坡研究人員證實(shí)一種代謝酶甘氨酸脫羧化酶(glycine decarboxylase, GLDC)對(duì)非小細(xì)胞肺癌(non-small-cell lung cancer)中腫瘤始發(fā)細(xì)胞(tumor-initiating cell, TIC)是比較關(guān)鍵的,。來自原發(fā)性非小細(xì)胞肺癌的腫瘤始發(fā)細(xì)胞表達(dá)高水平的癌干細(xì)胞因子LIN28B和甘氨酸脫羧化酶,，這兩者對(duì)于腫瘤始發(fā)細(xì)胞的生長(zhǎng)和腫瘤發(fā)生是必需的,。過表達(dá)甘氨酸脫羧化酶和其他甘氨酸/絲氨酸酶,，而不是催化上沒有活性的甘氨酸脫羧化酶，促進(jìn)細(xì)胞轉(zhuǎn)化和腫瘤發(fā)生。這就表明甘氨酸脫羧化酶是一種促進(jìn)正常細(xì)胞轉(zhuǎn)化為癌細(xì)胞的癌基因,。
研究人員還發(fā)現(xiàn)甘氨酸脫羧化酶促進(jìn)糖酵解和甘氨酸/絲氨酸代謝發(fā)生顯著的變化，從而導(dǎo)致嘧啶堿基代謝發(fā)生變化以便調(diào)節(jié)癌細(xì)胞增殖,。在診所中,，甘氨酸脫羧化酶的異常激活與肺癌病人更差的存活能力相關(guān)聯(lián)在一起，這樣人們可以利用甘氨酸脫羧化酶的表達(dá)情況來預(yù)測(cè)非小細(xì)胞肺癌的死亡率,。另外,，研究人員也在多種癌癥類型中觀察到異常的甘氨酸脫羧化酶表達(dá)。甘氨酸代謝和腫瘤發(fā)生之間的聯(lián)系可能為開發(fā)抗癌治療提供新的靶標(biāo),。(生物谷：towersimper編譯)
doi:10.1016/j.cell.2011.11.050
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Glycine Decarboxylase Activity Drives Non-Small Cell Lung Cancer Tumor-Initiating Cells and Tumorigenesis
Wen Cai Zhang, Ng Shyh-Chang, He Yang, Amit Rai, Shivshankar Umashankar, Siming Ma, Boon Seng Soh, Li Li Sun, Bee Choo Tai, Min En Nga, Kishore Kumar Bhakoo, Senthil Raja Jayapal, Massimo Nichane, Qiang Yu, Dokeu A. Ahmed, Christie Tan, Wong Poo Sing, John Tam, Agasthian Thirugananam, Monireh Soroush Noghabi, Yin Huei Pang, Haw Siang Ang, Paul Robson, Philipp Kaldis, Ross Andrew Soo, Sanjay Swarup, Elaine Hsuen Lim, Bing Lim
Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorigenesis. Overexpression of GLDC and other glycine/serine enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. We found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients, and aberrant GLDC expression is observed in multiple cancer types. This link between glycine metabolism and tumorigenesis may provide novel targets for advancing anticancer therapy.
