Genome Institute of Singapore more
Cancer remains one of the greatest scourges of human society and the multifarious ways cancer cells continuously mutate and evolve to elude physiological checks and controls present one of the greatest challenges in medicine.
Tumours are highly heterogeneous growth consisting of cancer cells intermingled with blood vessels and stromal cells. The cancer cell population itself is a constellation of different cell types contributing to the unique histopathological features of specific cancers.
In GIS, a dynamic complementation of expertise in cancer biology, stem cell and developmental biology, genomics technology and bioinformatics established the backdrop to some of our most exciting and new discoveries about the cellular and genetic drivers of tumour growth.
A careful tracking of clues from murine knockout models, for example of p63, has led us to the first description of residual embryonic cells that are likely the precursors of metaplasia, the earliest prequel to several aggressive epithelial cancers.
Most recently, we described the isolation of tumour initiating cells for lung cancer capable of proliferating, self renewal and differentiating. Deeper genomic analysis of the molecular signature of these cells led to the discovery of a previously unknown serine-glycine pathway recruited by many types of cancers. Our discovery heightens the increasing focus and excitement around cancer metabolism and metabolic targets. It also lends significant support to the hotly debated notion that cancer growth and phenotype is driven mainly by a subpopulation of cancer stem cells.
In GIS we are expanding our studies into several major cancers including colon, breast, liver and ovarian cancers together with our programme on isolating and characterising circulating tumour cells. Fuelling these studies are our discoveries of an increasing number of molecular drivers of cancer stem cells, such as PDK-1, and the application of exciting new development in single cell genomic technologies that allow deep inquiry into the DNA and RNAs of single cell. Our expectations are that research into the cellular and molecular biology of cancer stem cells will have a significant impact in improving the control and elimination of many cancers.
- Shuet Theng Lee1, Min Feng, Yong Wei, Zhimei Li, Yuanyuan Qiao1, Peiyong Guan, Meiyee Aau, Xia Jiang, Chew Hooi Wong, Kelly Huynh, Jinhua Wang, Juntao Li, K. Murthy Karuturi, Ern Yu Tan, Dave SB Hoon, Yibin Kang, Qiang Yu. Protein Tyrosine Phosphatase UBASH3B is Overexpressed in Triple-Negative Breast Cancer and Promotes Invasion and Metastasis. Proc Natl Acad Sci U S A, 2013 Jul 2;110(27):11121-6
- Tan J, Li Z, Lee PL, Guan P, Aau M, Lee ST, Feng M, Lim CZ, Lee EY, Wee ZN, Lim YC, Karuturi RK, Yu Q. "PDK1 Signaling Towards PLK1-Myc Activation Confers Oncogenic Transformation and Tumor Initiating Cell Activation and Resistance to mTOR-targeted Therapy." Cancer Discov 2013 Oct;3(10):1156-71
- Tam WL, Lu H, Buikhuisen J, Soh BS, Lim E, Reinhardt F, Wu ZJ, Krall JA, Bierie B, Guo W, Chen X, Liu XS, Brown M, Lim B, Weinberg RA. Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell. 2013 Sep 9;24(3):347-64.
- Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, Soh BS, Sun LL, Tai BC, Nga ME, Bhakoo KK, Jayapal SR, Nichane M, Yu Q, Ahmed DA, Tan C, Sing WP, Tam J, Thirugananam A, Noghabi MS, Pang YH, Ang HS, Mitchell W, Robson P, Kaldis P, Soo RA, Swarup S, Lim EH, Lim B. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell. 2012 Jan 20;148(1-2):259-72.
- Wang X, Ouyang H, Yamamoto Y, Kumar PA, Wei TS, Dagher R, Vincent M, Lu X, Bellizzi AM, Ho KY, Crum CP, Xian W, McKeon F. Residual embryonic cells as precursors of a Barrett's-like metaplasia. Cell. 2011 Jun 24;145(7):1023-35. doi: 10.1016/j.cell.2011.05.026.
- Jing Tan, Puay Leng Lee, Zhimei Li, Xia Jiang, Yaw Chyn Lim, Shing Chuan Hooi and Qiang Yu. B55β-associated PP2A complex controls PDK1-directed Myc signaling and modulates rapamycin sensitivity in colorectal cancer. Cancer Cell, 18:459-471, 2010.
- Guo G, Huss M, Tong GQ, Wang C, Li Sun L, Clarke ND, Robson P "Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst." Dev Cell 2010 Apr 20; 18(4) : 675-85.