Human CDH17 DNA contains 90138 bp composed of 18 exons (Gessner and Tauber, 2000; Wendeler et al., 2006).

Two transcripts (NM_001144663.1 and NM_004063.3) encode the same protein according to Entrez gene. 2499 bp open reading frame.

Cadherins are calcium-dependent cell-cell adhesion molecules which play important roles in organ development, the maintenance of tissue integrity and cancer development (Pokutta and Weis, 2007; Berx and van Roy, 2009). Cadherin 17 (CDH17) is a transmembrane glycoprotein with seven extracellular cadherin repeats. The cytoplasmic domain of human CDH17 only has 23 amino acids, whereas other classical cadherins contain 150 to 160 conserved amino acids forming complexes with catenins (Gessner and Tauber, 2000; Lee et al., 2010). CDH17 belongs to seven-domain (7D) cadherin subfamily which shares low sequence homology with the classical cadherins, such as E-cadherin. The structure difference of CDH17 makes this molecule unique among the known classical cadherin family members (Nollet et al., 2000; Angst et al., 2001). Recent work suggests its role in tumor progression and cancer prognosis (Liu et al., 2009).

In rats, CDH17 is expressed in the liver and small intestine (Berndorff et al., 1994). In mouse and human, CDH17 is highly expressed in the small intestine and colon (Angres et al., 2001; Takamura et al., 2004), but absent or very low level in other organs, such as liver, heart and kidney etc. It is also linked predominantly to a high incidence of tumorigenesis in the human liver, stomach, intestine and pancreas by displaying an aberrant expression in their cancerous state (Lee et al., 2010).

CDH17 is mainly localized on basolateral cell membrane. Overexpressed CDH17 can also be detected throughout the cytoplasm of liver cancer, gastric cancer and colon cells (Wong et al., 2003; Grötzinger et al., 2001; Takamura et al., 2004).

CDH17 was originally cloned from rat liver and identified as a novel cell adhesion molecule (Berndorff et al., 1994). Homotypic trans-interaction of CDH17 is dependent on extracellular calcium concentration. It might serve as a calcium-regulated adhesion switch (Wendeler et al., 2007). CDH17 is also reported as an intestinal peptide transporter. It facilitates the oral absorption of beta-lactam antibiotics and angiotensin-converting enzyme inhibitors from the intestine into enterocytes lining the luminal wall (Dantzig et al., 1994). Knockout CDH17 by a mutant CDH17 deficient mouse showed that CDH17 may also participate in B lymphocyte development (Ohnishi et al., 2005). Recent studies suggested CDH17 important roles in tumorigenesis. Overexpression CDH17 can promote tumor growth, while suppression of CDH17 inhibits cancer cell growth, migration and adhesion (Liu et al., 2009).

Human CDH17 shares ~20-30% sequence identity with other cadherin family members, such as cadherin-16 (30%), cadherin-13 (30%), and cadherin-1 (26%). It also shares ~79% identify with cyno-, mouse-, rat-cadherin-17.

No mutation has been reported for CDH17 so far.

Alternative mRNA splicing isoform of CDH17 was reported in hepatocellular carcinoma patient samples. The isoform skips exon 7 which leads to open reading frame shift. The mRNA isoform is associated with shorter overall survival time. The functions or mechanisms of the isoform in cancer are unclear (Wang et al., 2005).