Glycine Decarboxylase Activity Drives Non-Small Cell Lung Cancer Tumor-Initiating Cells and Tumorigenesis
2012; Cell Press; Volume: 148; Issue: 1-2 Linguagem: Inglês
10.1016/j.cell.2011.11.050
ISSN1097-4172
AutoresWen Cai Zhang, Ng Shyh‐Chang, Yang He, Amit Rai, Shivshankar Umashankar, Siming Ma, Boon-Seng Soh, Li Sun, Bee Choo Tai, Min En Nga, Kishore Bhakoo, Senthil Raja Jayapal, Massimo Nichane, Qiang Yu, Dokeu A. Ahmed, Christie Tan, Wong Poo Sing, John Kit Chung Tam, Thirugananam Agasthian, Monireh Soroush Noghabi, Yin Huei Pang, Haw Siang Ang, Wayne Mitchell, Paul Robson, Philipp Kaldis, Ross A. Soo, Sanjay Swarup, Elaine Hsuen Lim, Bing Lim,
Tópico(s)Epigenetics and DNA Methylation
ResumoSummaryIdentification 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.Graphical abstractGraphical AbstractHighlights► Non-small cell lung cancer (NSCLC) tumor-initiating cells express high levels of glycine decarboxylase (GLDC) ► GLDC is an oncogene that promotes cellular transformation ► GLDC activity regulates pyrimidine metabolism in cancer cells ► GLDC expression predicts mortality in NSCLC patients
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