Characterization of p120ctn, an Adherens Junction Protein With a Potential Role in Tumorigenesis and Cancer Metastasis

摘要

One of the deadliest and least understood aspects of cancer is metastasis. Before a tumor can metastasize, individual cells must acquire mutations which down-regulate adhesion to neighboring cells. Down-regulating components of the adherens junctions causes increased invasiveness and metastatic potential of tumors. Adherens junctions form around cadherins that interact homotypically to cadherins on neighboring cells. The cytoplasmic domain of cadherins interacts with a set of accessory proteins called catenins, which anchor cadherins to the actin cytoskeleton. pl20ctn, which was discovered in vertebrates, seems to be playing a regulatory rather than a structural role in adherens junctions. Before we can understand the role pl20ctn is playing in cancer, we must understand its normal cellular function. We have been studying pl20ctn in the fruitfly, Drosophila melanogaster. The objective of this research project is to characterize the role of pl20ctn by generating flies mutant for the p120 gene and characterizing them phenotypically and biochemically. We have generated 200 mutations in the pl20ctn region, and have identified a small chromosomal deletion that removes pl20ctn and affects only two complementation groups. We are testing these to determine whether either is the pl2Octn gene. We are also characterizing anti-pl20ctn antisera.