In search for the substrates of PRL-3, a protein encoded by PRL-3 gene implicated in colorectal cancer metastasis

• Main Authors: Chiang Yu Wei, 江囿瑋
• Other Authors: Chen Ji Hshiung
• Format: Others
• Language: en_US
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/87290066599206509066

碩士 === 慈濟大學 === 分子生物及細胞生物研究所 === 92 === Carcinogenesis is a multi-step process which involves many genetic changes and transforms normal cells into cancer cells. In previous studies, scientists have gained a better understanding of tumor progression. However, most of cancers eventually develop into metastatic one that contributes to the majority of cancer death. The specific molecular changes in tumor cells that promote metastasis process are unclear. Recent study reported that phosphatase of regenerating liver-3 (PRL-3) was the gene consistently overexpressed in colorectal cancer metastasis and was essentially undetectable in normal colorectal epithelia and intermediate expression in advanced primary cancers. PRL-3 is a protein tyrosine phosphatase, and it has prenylation motif at the C-terminus. In our study, PRL-3 was located at the cytoplasmic membrane and associated with some membrane structures which maybe involved in cell movement. When the prenylation motif was removed, it shifted into the nucleus and cytoplasm. In addition, it also played a causative role of promoting cell motility in PRL-3 stably expressing cells. These imply that PRL-3 maybe exert its functions by either cooperating with other proteins or alone to dephosphorylate its substrates contributing to cell migration. In order to find the substrates of PRL-3, we tried to use MALDI-TOF analysis to identify PRL-3 associated proteins in PRL-3 stably expressing cells and identified a possible substrate, rat liver regeneration-related protein LRRG01. It can provide orientation to investigate the molecular mechanism of PRL-3 in metastasis process.