Qi ZENG

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	Qi ZENG
	Lab Location: #3-02 email: mcbzengq@imcb.a-star.edu.sg tel: 65869664
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	Key Publications
	Ke Guo,* Jie Li,* Jing Ping Tang,* Cheng Peow Bobby Tan, Cheng William Hong, Abdul Qader O. Al-Aidaroos, Leyon Varghese, Caixia Huang, Qi Zeng (2011) Targeting Intracellular Oncoproteins with Antibody Therapy or vaccination *Science Transl Med* 3, 1-10, Sept 7 * equal first authors Abdul Qader O. Al-Aidaroos and Qi Zeng (Prospect, 2010) PRL-3 Phosphatase and Cancer Metastasis *J. Cell. Biol.* 111:1087–1098 Wang, H., Vardy, L., Tan, C.P., Loo, J.M., Guo, K., Li, J., Lim, S.G., Zhou, J., Chng, W.J., Ng, S.B., Li, H.X., and Zeng, Q. (2010) PCBP1 Suppresses the Translation of Metastasis-Associated PRL-3 Phosphatase. *Cancer Cell* 18, 52-62, July 13 Tang, J.P., Tan, C.P., Li, J., Siddique, M.M., Guo, K., Chan, S.W., Park, J.E., Tay, W.N., Huang, Z.Y., Li, W.C., Chen, J., and Zeng, Q. (2010) VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers. *Molecular Cancer* 9:128 Zeng Q. and W. Hong (2008) The emerging role of the Hippo pathway in cell contact inhibition, organ size control and cancer development in mammals (mini-review). *Cancer Cell* 13; 188-192. Guo, K., Li, J., Tang, J.P., Tan, C.P., Wang, H., and Zeng, Q. (2008) Monoclonal antibodies target intracellular PRL phosphatases to inhibit cancer metastases in mice. *Cancer Biology & Therapy* 7:752-759. Basak, S., Jacobs, S.B., Krieg, A.J., Pathak, N., Zeng, Q., Kaldis, P., Giaccia, A.J., Attardi, L.D. (2008) The metastasis-associated gene Prl-3 is a p53 target involved in cell cycle regulation. *Molecular Cell* 30:303-314. Wang, H.H., Quah, S.Y., Dong, J.M.,Manser, E., Tang, J.P. and Zeng, Q. (2007) PRL-3 downregulates PTEN expression and signals through PI3K to promote Epithelial-Mesenchymal Transition. *Cancer Research* 67:2922-2926. Guo, K., Li, J., Wang, H.H., Osato, M., Tang, J.P., Quah, SY., Gan, B.Q., and Zeng Q. (2006) PRL-3 initiates tumor angiogenesis by recruiting endothelial cells in vitro and in vivo. *Cancer Research* 66:9625-9635. Li, J., Guo, K., Koh, V.W.C., Tang, J.P., Gan, B.Q. Shi, H., Li, H.X. and Zeng, Q. (2005) Generation of PRL-3 and PRL-1 specific monoclonal antibodies as potential diagnostic markers for cancer metastases. *Clinical Cancer Research* 11:2195-2204 (Cover). Guo, K., Li, J., Tang, J.P., Koh, V., Gan, B.Q., and Zeng, Q. (2004) Catalytic Domain of PRL-3 Plays an Essential Role in Tumor Metastasis; Formation of PRL-3 tumors inside the blood vessels. *Cancer Biology & Therapy* 3:945-951 (Cover). Zeng, Q., Dong, J.M., Guo, K., Li, J., Tan, H.X., Koh, V., Pallen, C.J., Manser, E., and Hong, W. (2003) PRL-3 and PRL-1 promote cell migration, invasion, and metastasis. Cancer Research* 63:2716-2722 (Correspondence). Si, X., Zeng, Q., Ng, C.H., Hong, W., and Pallen, C.J. (2001) Interaction of Farnesylated PRL-2, a protein Tyrosine Phosphatase, with the Beta Subunit of Geranylgeranyltransferase II. J. Biol. Chem.* 276:32875-32882. Zeng, Q., Si, X., Horstmann, H., Xu, Y., Tan, Y.H., Hong, W. and Pallen, C.J. (2000) Prenylation-dependent Association of Protein-tyrosine Phosphatases PRL-1, -2, and -3 with the Plasma Membrane and the Early Endosome. *J. Biol. Chem. 274:21444-21452. Zeng, Q., Hong, W., and Tan, Y.H. (1998) Mouse PRL-2 and PRL-3, two potentially prenylated protein tyrosine phosphatases homologous to PRL-1. Biochem. Biophys. Res. Commun.* 244:421-427.
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			Qi ZENG
			Qi ZENG obtained her BSc from Xiamen University (China), MSc from SUNY (USA) and PhD from IMCB, NUS (Singapore) in 1993 . She used transgenic mice in her graduate studies to learn molecular mechanisms governing human hypertension. She genetically engineered the first transgenic rat in Asia for a San Diego biotech firm to study human diabetes. Her success story was appeared in Fortune Magazine (USA, Oct. 1991). In 1998, she identified a protein tyrosine phosphatase - PRL-3, which has been implicated in metastasis of colorectal cancer cells. As a Principal Investigator, she has made high-impact contributions to the understanding of the molecular basis underlying PRL-3-induced cancer metastasis. She has been using animal models to study human diseases for more than 20 years. She is also an adjunct Associate Professor in Department of Biochemistry, NUS. The group has been awarded a Flagship grant of $3.1 million in 2009 from Exploit Technologies Pte Ltd (ETPL, A*STAR) for her anticancer therapy in mouse model: http://www.imcb.a-star.edu.sg/newsarchive/090309a.php.

			PRL-3 and Cancer Metastasis
			Dr Zeng’s laboratory works on both Basic and Translational Research: Basic Research: PRL-3 phosphatase contributes to human cancers PRL-3 phosphatase was identified in 1998 (Zeng et al., 1998). Professor Bert Vogelstein’s laboratory first found that PRL-3 was upregulated in colorectal cancer metastasis (Saha et al., 2001). PRL-3 was then demonstrated to play a causal role in promoting cancer metastasis in mice (Zeng et al., 2003). Generating specific PRLs monoclonal antibodies, the group further showed that PRL-3 protein is overexpressed in several primary human cancers examined by immunohistochemistry (Li et al., 2005). Subsequently, many other groups demonstrated that PRL-3 transcript or protein is often overexpressed in various types of human cancer and its expression is associated with poor prognosis. Two important reviews summarize the work on PRL-3 (Bessette and Pallen, 2008; Stephens et al., 2005). The group has found that PRL-3 could trigger angiogenesis and establish microvasculature by recruiting endothelial cells (Guo t al., 2006). They have further showed that PRL-3 could downregulate PTEN expression and signal through PI3K pathway to promote Epithelial-Mesenchymal Transition (EMT) (Wang et al., 2007). Most recently, the group identifies PolyC-RNA-binding protein 1 (PCBP1) as an upstream regulator of PRL-3 translation and reveals a molecular mechanism responsible for the regulation of PRL-3 expression in cancer. The inverse correlation between PCBP1 and PRL-3 protein levels in several human cancers suggests that PCBP1-mediated PRL-3 regulation is of physiological and clinical relevance. The axis of PCBP1→PRL-3→AKT may be a pathway in controlling cancer progression. The finding of PCBP1 as a tumor suppressor is highly significant as a similar mechanism may be regulating other cancer genes (Wang et al., 2010).
			Figure legend: A. Immunohistochemistry analyses on a human colon cancer. The intact section showed that PRL-3 protein was expressed in cancerous but not in normal epithelia. A red arrowhead indicates the transition area between cancerous and normal colon tissue. Scale Bar, 100 mm B. A working model for the action of PCBP1 in regulating the translation of the PRL-3 mRNA. When PCBP1 protein levels are high, PCBP1 binds to the 6-base GC-motifs located at the 5’UTR of the PRL-3 mRNA, resulting in repression of PRL-3 translation (upper panel); while when PCBP1 protein levels are low, PCBP1 does not bind to the GC-motifs, and it releases the inhibition of PRL-3 translation. The PRL-3 translation then proceeds with high efficiency (lower panel). Translational Research: Inhibiting PRL-3 associated cancer metastasis in mice The group has been awarded a Flagship grant of $3.1 million from ETPL in 2009. The prestigious award will support Dr. Zeng’s research to explore a unique approach of inhibiting human cancer metastases by unconventional antibody therapy as they demonstrated that PRL-1 and PRL-3 mAbs can inhibit experimental cancer metastasis of cancer cells expressing the respective antigen using antibodies against PRL-1 or PRL-3 phosphatase. Recently, the group reported a new concept of ‘Targeting Intracellular Oncoproteins with Antibody Therapy or Vaccination’ (Guo at el., Science Translational Medicine, 2011) with Perspective; their findings were highlighted in Science main website on 7 Sept. 2011. ETPL expects her team to generate several humanized PRLs’ antibodies as therapeutic agents to treat human cancers that are associated with overexpression of PRL-phosphatases. Several pharmaceutical and biotech companies have expressed strong interests in the proposed pre-clinical studies using their mouse model. A. PRL-3 and PRL-1 mAbs specifically inhibit the formation of metastatic lung tumors by cells expressing the respective antigen. One million CHO-EGFP-PRL-3 expressing cells were injected into nude mice via the tail vein. Mice were either untreated (a, n = 10) or PBS-treated (b, n = 10), or treated with two unrelated antibodies (c, n = 5; d, n = 5). PRL-3 mAb 223 is in the form of purified IgG (e) or ascitic fluid (g); Lungs were dissected out on day 15 post-injection and photographed under fluorescence microscopy. B. The total numbers of tumors in A are quantified in the Y axis as the average of tumor lesions from each group, while the X axis displays the various groups of mice with different treatments.