Abstract 1460: AKAP12 regulates melanoma tumor growth and metastasis

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Skin cancer, which accounts for at least half of all cancers in the United States, is predicted to affects 1 in 5 Americans in their lifetime. Melanoma, the most serious form of skin cancer, is also the leading cause of all skin cancer deaths. This study demonstrates that AKAP12 (SSeCKS, AKAP250, gravin), a hypoxia-inducible scaffold protein, is considerably increased at the protein and RNA level in melanoma cell lines. In addition, there is a significant increase in RNA expression in primary and metastatic tumors when compared to normal specimens, as well as patients with poor prognosis, as measured by diminished 5- year survival. AKAP12 functions to dock many kinases and signaling proteins that regulate cell adhesion, spreading and migration, including: PKC, Src and F-actin. Since these processes are critical for tumor cell metastasis, we hypothesize that AKAP12 could be a central regulator of cancer progression. Stable knockdown of AKAP12 in two melanoma cell lines demonstrate decreases in invasion, migration and clonogenic potential in vitro, as well reduced colony forming abilities in conditions requiring anchorage-independent growth in soft agar. In vivo studies in a metastatic model of melanoma demonstrate a statistically significant decrease in tumors within the lungs of the AKAP12 knockdown groups, highlighting the importance of AKAP12 in metastatic disease. An orthotopic model also demonstrates decreased primary tumor growth and metastatic potential in mice injected with AKAP12 knocked down cells. Additionally, changes in cell morphology characteristic of increased motility and invasiveness are seen in cells containing AKAP12 but not those in which it had been knocked down. While this scaffold protein has been found to act as a tumor suppressor in several tissue types (lung, colon, prostate), we have uncovered its novel oncogenic properties in metastatic melanoma. 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 1460. doi:10.1158/1538-7445.AM2011-1460