TY - JOUR
T1 - Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis
AU - Zhang, Wen Cai
AU - Ng, Shyh Chang
AU - Yang, He
AU - Rai, Amit
AU - Umashankar, Shivshankar
AU - Ma, Siming
AU - Soh, Boon Seng
AU - Sun, Li Li
AU - Tai, Bee Choo
AU - Nga, Min En
AU - Bhakoo, Kishore Kumar
AU - Jayapal, Senthil Raja
AU - Nichane, Massimo
AU - Yu, Qiang
AU - Ahmed, Dokeu A.
AU - Tan, Christie
AU - Sing, Wong Poo
AU - Tam, John
AU - Thirugananam, Agasthian
AU - Noghabi, Monireh Soroush
AU - Pang, Yin Huei
AU - Ang, Haw Siang
AU - Robson, Paul
AU - Kaldis, Philipp
AU - Soo, Ross Andrew
AU - Swarup, Sanjay
AU - Lim, Elaine Hsuen
AU - Lim, Bing
PY - 2012/1/20
Y1 - 2012/1/20
N2 - 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.
AB - 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.
UR - https://doi.org/10.1016/j.cell.2012.02.024
U2 - 10.1016/j.cell.2011.11.050
DO - 10.1016/j.cell.2011.11.050
M3 - Article
C2 - 22225612
AN - SCOPUS:84856087055
SN - 0092-8674
VL - 148
SP - 259
EP - 272
JO - Cell
JF - Cell
IS - 1-2
ER -
