Abstract 5269: Mechanistic insights into regulation of metastasis by Sipa1

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.5269-5269
• Main Authors: Geiger, Thomas R., Mattaini, Katie, Williams, Mia, Walker, Renard, Alsarraj, Jude, Borges, Rosan Nieves, Hunter, Kent
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-5269

Metastasis is the major cause for morbidity and mortality of cancer patients. Still, the molecular mechanisms underlying metastasis are incompletely understood. Conceivably, a better knowledge of the metastatic process will enable the design of better treatments for cancer patients in the future. Previously, we have shown that genetic background has a strong influence on metastasis susceptibility in breast cancer mouse models. Single nucleotide polymorphisms (SNP) in the Sipa1 gene are associated with metastasis in mice and human breast cancer patients. Consistent with this observation, we have shown that Sipa1 regulates metastasis in breast cancer cells; however, the molecular mechanisms remain largely unknown. We identified several potential binding partners of SIPA1 in a yeast-two-hybrid screen, and confirmed interactions of SIPA1 with BRD4, RRP1B and SUN2 in subsequent experiments. Our analysis suggests that several complexes of SIPA1 exist in different compartments of the cell. A structure-function analysis that we have begun to carry out indicates that Sipa1 regulates metastasis in several ways, depending on its interaction partners and subcellular localization. Furthermore, the enzymatic GTPase-activating function of Sipa1 appears to play a critical role in regulating metastasis. These results could facilitate developing novel therapeutic approaches for the treatment of metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5269. doi:10.1158/1538-7445.AM2011-5269