Author/Authors :
Wen Cai Zhang، نويسنده , , Ng Shyh-Chang، نويسنده , , He Yang، نويسنده , , Amit Rai، نويسنده , , Shivshankar Umashankar، نويسنده , , Siming Ma، نويسنده , , Boon Seng Soh، نويسنده , , Li Li Sun، نويسنده , , Bee Choo Tai، نويسنده , , Min En Nga، نويسنده , , Kishore Kumar Bhakoo، نويسنده , , Senthil Raja Jayapal، نويسنده , , Massimo Nichane، نويسنده , , Qiang Yu، نويسنده , , Dokeu A. Ahmed، نويسنده , , Christie Tan، نويسنده , , Wong Poo Sing، نويسنده , , John Tam، نويسنده , , Agasthian Thirugananam، نويسنده , , Monireh Soroush Noghabi، نويسنده , , et al.، نويسنده ,
Abstract :
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.
