Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis

Zhang, Wen Cai ; Ng, Shyh Chang ; Yang, He ; Rai, Amit ; Umashankar, Shivshankar ; Ma, Siming ; Soh, Boon Seng ; Sun, Li Li ; Tai, Bee Choo and Nga, Min En , et al. (2012) In Cell 148(1-2). p.259-272
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,... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
in
Cell
volume
148
issue
1-2
pages
259 - 272
publisher
Cell Press
external identifiers
  • scopus:84856087055
  • pmid:22225612
ISSN
0092-8674
DOI
10.1016/j.cell.2011.11.050
language
English
LU publication?
no
id
a8f64de7-66b0-4048-8454-0ec02f8c8486
date added to LUP
2019-09-18 14:01:10
date last changed
2024-06-13 04:24:07
@article{a8f64de7-66b0-4048-8454-0ec02f8c8486,
  abstract     = {{<p>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.</p>}},
  author       = {{Zhang, Wen Cai and Ng, Shyh Chang and Yang, He and Rai, Amit and Umashankar, Shivshankar and Ma, Siming and Soh, Boon Seng and Sun, Li Li and Tai, Bee Choo and Nga, Min En and Bhakoo, Kishore Kumar and Jayapal, Senthil Raja and Nichane, Massimo and Yu, Qiang and Ahmed, Dokeu A. and Tan, Christie and Sing, Wong Poo and Tam, John and Thirugananam, Agasthian and Noghabi, Monireh Soroush and Pang, Yin Huei and Ang, Haw Siang and Robson, Paul and Kaldis, Philipp and Soo, Ross Andrew and Swarup, Sanjay and Lim, Elaine Hsuen and Lim, Bing}},
  issn         = {{0092-8674}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1-2}},
  pages        = {{259--272}},
  publisher    = {{Cell Press}},
  series       = {{Cell}},
  title        = {{Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis}},
  url          = {{http://dx.doi.org/10.1016/j.cell.2011.11.050}},
  doi          = {{10.1016/j.cell.2011.11.050}},
  volume       = {{148}},
  year         = {{2012}},
}