Abstract 4933: Functional properties of PPFIA1, located at the 11q13 amplification region, in epithelial cancer cells.

PPFIA1 (liprin α1) is a member of the liprin (LAR protein-tyrosine phosphatase-interacting protein) family and is located at the 11q13 amplification region, which is one of the most common amplicons in multiple epithelial cancers. In squamous cell carcinoma of head and neck (HNSCC), this amplification occurs in 30-50% of the cases. In epithelial cancers, the size and structure of 11q13 amplicon is complex and consists of multiple amplicon cores that differ between different tumor types. In HNSCC, the amplicon core contains 10 genes that are amplified in cases with 11q13 amplification. This region contains well-established oncogenes, such as CCND1 and CTTN (cortactin), yet the role of several genes in this region is unknown. Our aim is to study the role of PPFIA1, which has recently been found to be involved in cell motility, modeling of the cell edge dynamics and axon guidance. PPFIA1 is amplified and overexpressed in several epithelial cancers, but the role of it is controversial. PPFIA1 is required for breast and cervical cancer cell invasion, but in contrast depletion of it results in increased invasion of HNSCC cells. We have overexpressed liprin α1 and cortactin in HNSCC cells with no 11q13 amplification and related phenotypes have been analysed in in vitro assays. Migration assays using matrigel coated inserts have shown that overexpression of cortactin increases invasive properties of the HNSCC cells with no 11q13 amplicon whereas liprin α1 has an opposite effect. We have also shown that liprin α1 localizes with cortactin in same vesicular structures, but they do not show physical interaction. Our aim is now to explore the molecular mechanisms behind these findings to assess the role of liprin α1 in vesicular transport and cell motility. We are also carrying out immunoprecipitation and mass spectrometry analyses to identify novel interaction partners for this protein. Our study will provide novel information on the potential specialized functions of liprin α1 in different epithelial cancers, which is likely to improve our understanding on the functional role of 11q13 amplification in malignant potential of cancer cells. Citation Format: Henna Pehkonen, Tatiana Lepikhova, Riku Louhimo, Nina Peitsaro, Misa Imai, Rafael Martinez, Juha Kleftsrom, Sampsa Hautaniemi, Outi Monni. Functional properties of PPFIA1, located at the 11q13 amplification region, in epithelial cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4933. doi:10.1158/1538-7445.AM2013-4933