Abstract 1981: Tumor suppressor functions of the Src-like adaptor protein (SLAP) in colorectal cancer cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.1981-1981
• Main Authors: Naudin, Cécile, Leroy, Cédric, Sirvent, Audrey, Simon, Valérie, Bourgaux, Jean-François, Robert, Bruno, Pannequin, Julie, Hollande, Frédéric, Roche, Serge
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-1981

Background : The cytoplasmic tyrosine kinase Src is frequently deregulated in colorectal cancer (CRC) and this deregulation is implicated in tumour growth and in the induction of metastasis. How Src is activated in this cancer has not been clearly established. In contrast to Ras, Src activating mutations are rare events, suggesting the existence of alternative mechanisms for the induction of Src oncogenic activity. Here, we addressed whether Src deregulation involves inhibition of its negative regulators, including the Src-Like Adaptor Protein (SLAP). Experimental procedures : SLAP expression was analyzed in colon cancer cells and in microdissected tissue samples of patients with CRC. The effect of SLAP was analyzed on the capacity of CRC cells to grow in soft agar and to induce tumours once engrafted in nude mice. The effect of SLAP on the invasive properties of CRC cells was investigated in vitro using Matrigel Boyden chamber assays, as well as in vivo following injection in the spleen of Balb-c mice. Results : We found that SLAP is expressed in the healthy colon and that its expression is reduced in 60% of CRC biopsies tested. Moreover, we showed that SLAP overexpression dramatically reduced the capacity of CRC cells to induce primary tumours and liver metastases in vivo. Conversely, SLAP knock-down in early-stage CRC cells led to a remarkable induction of liver metastasis in mice. This novel function of SLAP required its myristoylation site as well as intact SH3 and SH2 domains. A proteomic approach is under way to identify SLAP partners involved in this tumor suppressor activity. Conclusions: Our results suggest that, in addition to lymphocytes, SLAP also regulates transforming properties of CRC cells. We hypothesize that SLAP negatively regulates oncogenic signalling initiated by tyrosine kinases including Src. 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 1981. doi:10.1158/1538-7445.AM2011-1981