Abstract 4327: Loss of the APC tumor suppressor alters breast cancer cell migration and invasion

Abstract

Abstract Metastasis is responsible for the majority of deaths attributable to cancer, but the molecular events that drive the metastatic phenotype are not completely understood. The adenomatous polyposis coli (APC) tumor suppressor is frequently inactivated in colorectal cancer as well as other tumor types, such as breast cancer, and has been implicated specifically in early tumor progression. However, it is not known whether APC also plays an important role in the later stages of cancer pathogenesis, including invasion and metastasis. Preliminary data indicated that transient knockdown of APC in 4T07 mouse mammary tumor cells led to marked morphological changes from mesenchymal-like to epithelial-like phenotypes, leading to the hypothesis that APC can effect the mesenchymal-to-epithelial transition and may alter cancer metastasis. To test this hypothesis, 4T07 cells were stably infected with lentiviral APC short-hairpin (sh)RNAs, and knockdown of APC expression was verified by quantitative real-time PCR and immunofluorescence (IF) with an APC antibody. We found that APC depletion altered the mesenchymal morphology of these cells to a more epithelial phenotype. The localization of β-catenin at the ends of cell protrusions was dependent on APC; however, APC knockdown did not result in cytosolic or nuclear accumulation of β-catenin. Consistent with the observed morphology change, APC depletion significantly impaired the ability of 4T07 cells to migrate in wound-filling assays and invade through a Matrigel-coated membrane. Together, these results suggest that APC loss impacts the morphology, migration and invasion of breast cancer cells, all key features of metastatic capacity. Current efforts are aimed at uncovering the mechanism by which APC alters these properties and translating these findings to our understanding of breast cancer metastasis in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4327. doi:1538-7445.AM2012-4327