Loss of Coxsackie and adenovirus receptor downregulates α-catenin expression

The Coxsackie and adenovirus receptor (CAR) was first characterised as a viral attachment site on the surface of epithelial cells and was later identified as an integral component of the tight junction complex (Coyne and Bergelson, 2005). In several human carcinomas, particularly in more advanced stages, a reduced CAR presence was found, partially associated with loss of tumour differentiation, increased infiltration, and poor prognosis (Sachs et al, 2002; Matsumoto et al, 2005; Korn et al, 2006; Buscarini et al, 2007; Okegawa et al, 2007; Anders et al, 2009). On the basis of data from studies in cell lines, it has been speculated that loss of CAR promotes the proliferation, migration, and invasion of cancer cells (Okegawa et al, 2000, 2001; Bruning and Runnebaum, 2003, 2004; Huang et al, 2005; Wang et al, 2005). These phenomena are believed to result from an impaired intercellular adhesion (Okegawa et al, 2000; Bruning and Runnebaum, 2004; Wang et al, 2005). Recently, it has been shown that CAR interacts with microtubules, and therefore contributes to the cytoskeletal equilibrium and inhibits cell migration (Fok et al, 2007). A more detailed insight into the mechanisms underlying the influence of CAR on cancer cell pathobiology, however, is lacking. Aiming to further elucidate genes that facilitate the proposed function of CAR in cancer, we determined differential gene expression after CAR knockdown in the human colon cancer cell line DLD1 and assessed the functional impact of the strongest regulated gene α-catenin.