Qi ZENG obtained her BSc from Xiamen University (China), MSc from SUNY (USA) and PhD from IMCB (NUS, Singapore). She used transgenic mice in her graduate studies to learn molecular mechanisms governing tissue/cell-specific gene expression. She then developed transgenic rat technique in 1990. In addition, she has identified two tyrosine phosphatases, PRL-2 and 3, which have recently 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 metastasis.

The first phosphatase induced in regenerating liver (PRL-1) was identified in 1994. In 1998, the PRL-1 sequence was used to search EST databases, leading to the identification of two more members, PRL-2 and PRL-3. Among 107 human phosphatases, PRL-1, PRL-2 and PRL-3 represent an oncogenic PRL-family with a C-terminal prenylation motif.

PRL-3 is enriched in membrane structures highly related to cell movement and cell migration. Using serial analysis of gene expression (SAGE), Dr. Bert Vogelstein’s team in Johns Hopkins reported that the PRL-3 mRNA is consistently elevated in metastatic samples derived from colorectal cancers. Colorectal cancer is the second-leading cause of cancer-related deaths in the United States. It is also the second most common cancer in Singapore.

This group is studying how PRL-3 promotes colon cancer metastasis. They hope to gain a better understanding of the molecular basis of metastasis and to learn more about how this gene contributes to the disease. They have demonstrated that the overexpression of PRL-3 is sufficient to cause metastasis in an experimental animal model. PRL-3 and PRL-1 promote cell migration, invasion, and metastasis. Recently, they have also demonstrated that the metastasis-promoting property is dependent on PRL-3’s phosphatase activity. The catalytic domain of PRL-3 plays an essential role in tumour metastasis. They have made a surprising observation of tumors growing inside of blood vessels, a phenomenon that was described as “dramatic and novel”.

Currently, they have successfully generated specific mouse monoclonal antibodies against PRL-3 and PRL-1. The PRL-3 specific antibodies were used to examine 282 human colorectal cancer samples. PRL-3 overexpression was shown in approximately 11% of primary colorectal cancer samples. This indicates that PRL-3 may play a priming role in cancer metastasis and that patients with a PRL-3 positive signal might have a higher risk of cancer metastasis later in life. In recent studies, PRL-3 or PRL-1 was also detected in other types of cancer, which suggests that PRL-1 might play a similar role in metastasis of different types of cancer. Therefore, PRLs can be used as diagnostic markers for prognosis. Early attention to these patients is important for cancer treatment and prevention. Monoclonal antibodies to these PRLs will be essential in bridging the laboratory and the clinic and will be further exploited for applications in clinical research and diagnosis of human cancer. To investigate the role of PRL-3 in tumor angiogenesis, they found PRL-3 could trigger angiogenesis and establish the microvasculature by recruiting endothelial cells. To examine the role of PRL-3 in tumor cell signaling, they demonstrate that PRL-3 could downregulate PTEN expression and signal through PI3K pathway. Much more work remains to be done to understand how PRL-3 is linked to cancer metastasis.