Glycine Decarboxylase Activity Drives Non-Small Cell Lung Cancer Tumor-Initiating Cells and Tumorigenesis

被引：541

作者：

Zhang, Wen Cai ^{[1
,2
]}

Shyh-Chang, Ng ^{[2
]}

Yang, He ^{[3
]}

Rai, Amit ^{[5
]}

Umashankar, Shivshankar ^{[5
,6
]}

Ma, Siming ^{[2
]}

Soh, Boon Seng ^{[2
]}

Sun, Li Li ^{[2
]}

Tai, Bee Choo ^{[10
]}

Nga, Min En ^{[8
]}

Bhakoo, Kishore Kumar ^{[11
]}

Jayapal, Senthil Raja ^{[12
,13
]}

Nichane, Massimo ^{[2
]}

Yu, Qiang ^{[2
]}

Ahmed, Dokeu A. ^{[4
]}

Tan, Christie ^{[4
]}

Sing, Wong Poo ^{[9
]}

Tam, John ^{[9
]}

Thirugananam, Agasthian ^{[14
]}

Noghabi, Monireh Soroush ^{[2
]}

Pang, Yin Huei ^{[8
]}

Ang, Haw Siang ^{[3
]}

Robson, Paul ^{[2
]}

Kaldis, Philipp ^{[12
,13
]}

Soo, Ross Andrew ^{[3
,7
]}

Swarup, Sanjay ^{[5
,6
]}

Lim, Elaine Hsuen ^{[1
,7
,15
]}

Lim, Bing ^{[2
,16
]}

机构：

[1] Tan Tock Seng Hosp, Dept Resp Med, Singapore 308433, Singapore

[2] Genome Inst Singapore, Singapore 138672, Singapore

[3] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117456, Singapore

[4] Tan Tock Seng Hosp, Dept Thorac Surg, Singapore 308433, Singapore

[5] Natl Univ Singapore, Dept Biol Sci, Metabolites Biol Lab, Singapore 117543, Singapore

[6] Natl Univ Singapore, T Lab Bldg TL, NUS Environm Res Inst NERI, Singapore 117411, Singapore

[7] Natl Univ Singapore Hosp, Dept Haematol Oncol, Singapore 119074, Singapore

[8] Natl Univ Singapore Hosp, Dept Pathol, Singapore 119074, Singapore

[9] Natl Univ Singapore Hosp, Dept Thorac Surg, Singapore 119074, Singapore

[10] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 117597, Singapore

[11] Singapore BioImaging Consortium SBIC, Lab Mol Imaging LMI, Translat Mol Imaging Grp TMIG, Singapore 138667, Singapore

[12] Inst Mol & Cell Biol, Cell Div, Singapore 138673, Singapore

[13] Inst Mol & Cell Biol, Canc Lab PRK, Singapore 138673, Singapore

[14] Natl Canc Ctr, Dept Thorac Surg, Singapore 169610, Singapore

[15] Natl Canc Ctr, Dept Med Oncol, Singapore 169610, Singapore

[16] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

来源：

CELL | 2012年 / 148卷 / 1-2期

关键词：

STEM-CELL; CLEAVAGE SYSTEM; IDENTIFICATION; METABOLISM; EXPRESSION; PROTEIN;

D O I：

10.1016/j.cell.2011.11.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：259 / 272

页数：14

共 43 条

[1]

[Anonymous], CA CANC J CLIN, DOI DOI 10.3322/CAAC.20107

[2] Aquaporin-3 expression in human fetal airway epithelial progenitor cells [J].

Avril-Delplanque, A ;

Casal, I ;

Castillon, N ;

Hinnrasky, J ;

Puchelle, E ;

Péault, B .

STEM CELLS, 2005, 23 (07) :992-1001

[3] Nucleotide Deficiency Promotes Genomic Instability in Early Stages of Cancer Development [J].

Bester, Assaf C. ;

Roniger, Maayan ;

Oren, Yifat S. ;

Im, Michael M. ;

Sarni, Dan ;

Chaoat, Malka ;

Bensimon, Aaron ;

Zamir, Gideon ;

Shewach, Donna S. ;

Kerem, Batsheva .

CELL, 2011, 145 (03) :435-446

[4] Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 [J].

Boiko, Alexander D. ;

Razorenova, Olga V. ;

van de Rijn, Matt ;

Swetter, Susan M. ;

Johnson, Denise L. ;

Ly, Daphne P. ;

Butler, Paris D. ;

Yang, George P. ;

Joshua, Benzion ;

Kaplan, Michael J. ;

Longaker, Michael T. ;

Weissman, Irving L. .

NATURE, 2010, 466 (7302) :133-U155

[5] The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth [J].

Christofk, Heather R. ;

Vander Heiden, Matthew G. ;

Harris, Marian H. ;

Ramanathan, Arvind ;

Gerszten, Robert E. ;

Wei, Ru ;

Fleming, Mark D. ;

Schreiber, Stuart L. ;

Cantley, Lewis C. .

NATURE, 2008, 452 (7184) :230-U74

[6] A novel normalization method for effective removal of systematic variation in microarray data [J].

Chua, SW ;

Vijayakumar, P ;

Nissom, PM ;

Yam, CY ;

Wong, VVT ;

Yang, H .

NUCLEIC ACIDS RESEARCH, 2006, 34 (05)

[7] Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth [J].

Civenni, Gianluca ;

Walter, Anne ;

Kobert, Nikita ;

Mihic-Probst, Daniela ;

Zipser, Marie ;

Belloni, Benedetta ;

Seifert, Burkhardt ;

Moch, Holger ;

Dummer, Reinhard ;

van den Broek, Maries ;

Sommer, Lukas .

CANCER RESEARCH, 2011, 71 (08) :3098-3109

[8] Primary Tumor Genotype Is an Important Determinant in Identification of Lung Cancer Propagating Cells [J].

Curtis, Stephen J. ;

Sinkevicius, Kerstin W. ;

Li, Danan ;

Lau, Allison N. ;

Roach, Rebecca R. ;

Zamponi, Raffaella ;

Woolfenden, Amber E. ;

Kirsch, David G. ;

Wong, Kwok-Kin ;

Kim, Carla F. .

CELL STEM CELL, 2010, 7 (01) :127-133

[9] Cancer-associated IDH1 mutations produce 2-hydroxyglutarate [J].

Dang, Lenny ;

White, David W. ;

Gross, Stefan ;

Bennett, Bryson D. ;

Bittinger, Mark A. ;

Driggers, Edward M. ;

Fantin, Valeria R. ;

Jang, Hyun Gyung ;

Jin, Shengfang ;

Keenan, Marie C. ;

Marks, Kevin M. ;

Prins, Robert M. ;

Ward, Patrick S. ;

Yen, Katharine E. ;

Liau, Linda M. ;

Rabinowitz, Joshua D. ;

Cantley, Lewis C. ;

Thompson, Craig B. ;

Heiden, Matthew G. Vander ;

Su, Shinsan M. .

NATURE, 2009, 462 (7274) :739-U52

[10] In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells [J].

Dontu, G ;

Abdallah, WM ;

Foley, JM ;

Jackson, KW ;

Clarke, MF ;

Kawamura, MJ ;

Wicha, MS .

GENES & DEVELOPMENT, 2003, 17 (10) :1253-1270

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