Disease relevance of CDH17

• Cadherin switching has also been implicated in tumorigenesis, particularly in metastasis [1].
• LI-cadherin: a marker of gastric metaplasia and neoplasia [2].
• Well differentiated gastric carcinomas showed intense staining for LI-cadherin while undifferentiated carcinomas showed only weak diffuse cytoplasmic staining [2].
• Thus LI-cadherin represents a new, reliable, and powerful marker molecule for early detection of gastric intestinal metaplasia and well differentiated adenocarcinomas [2].
• CONCLUSIONS: Over-expression of LI-cadherin was frequently detected in liver cancer patients [3].

Psychiatry related information on CDH17

• Anti-phospho-threonine 212/phospho-serine 214 (HPT-1), anti-phospho-threonine 231/phospho-serine 235 (HPT-101) and their biotinylated derivatives were shown to be sensitive markers for the immunohistochemical detection of neuropathological alterations during Alzheimer's disease [4].

High impact information on CDH17

• The amino acid sequence deduced from the complementary DNA sequence of the cloned gene indicated that this transport-associated protein shares several conserved structural elements with the cadherin superfamily of calcium-dependent, cell-cell adhesion proteins [5].
• Features such as a large repertoire of homotypically interacting cadherins, rapid assembly and disassembly, and a connection to a force-generating actin cytoskeleton make cadherin-mediated junctions ideal structures for the execution of complex changes in cell and tissue morphology during development [6].
• A major form of animal cell-cell adhesion results from the dynamic association of cadherin molecules, cytosolic catenins and actin microfilaments [7].
• Tissue morphogenesis during development is dependent on activities of the cadherin family of cell-cell adhesion proteins that includes classical cadherins, protocadherins, and atypical cadherins (Fat, Dachsous, and Flamingo) [8].
• Thus, CD8(+)/CD103(+) tumor-reactive T lymphocytes infiltrating epithelial tumors most likely play a major role in antitumor cytotoxic response through alpha(E)beta(7)-E-cadherin interactions [9].

Chemical compound and disease context of CDH17

• The role of alpha E beta 7 integrin (CD103) and E-cadherin in epidermotropism in cutaneous T-cell lymphoma [10].

Biological context of CDH17

• CONCLUSION: The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a genetic susceptibility factor for the development of HCC in a Chinese population [11].
• We previously showed that aberrant mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was triggered by the specific constellation of two CDH17 single nucleotide polymorphisms (651T and IVS6+35G) [11].
• BACKGROUND: The atypical Fat cadherin has long been known to control cell proliferation and organ size in Drosophila, but the mechanism by which Fat controls these processes has remained elusive [12].
• CONCLUSIONS: To detect early metaplastic changes in the gastric mucosa, LI-cadherin has a sensitivity superior to sucrase-isomaltase and conventional histology and comparable with that of villin [2].
• Clinically, those patients who harbored the alternative splicing of LI-cadherin were strongly associated with shorter overall survival time (P < 0.01) as well as higher incidences of tumor recurrences and venous infiltration (both P < 0.05) after hepatectomy [3].

Anatomical context of CDH17

• Lymph node metastasis was significantly associated with the expression of LI-cadherin (p=0.038) [13].
• The mRNA of LI-cadherin was highly expressed in tumor as compared to non-cancerous mucosa [13].
• Among the cell lines, LI-cadherin expression was detected in a differentiated phenotype, but not in dedifferentiated phenotypes [14].
• Indeed, we found that although tumor-specific CD103(+) TIL-derived cytotoxic T lymphocyte (CTL) clones are able to kill E-cadherin(+)/intercellular adhesion molecule 1(-) autologous tumor cells, CD103(-) peripheral blood lymphocyte (PBL)-derived counterparts are inefficient [9].
• In this report, we demonstrate that the interaction of epithelial cell marker E-cadherin with integrin alpha(E)(CD103)beta(7), often expressed by tumor-infiltrating lymphocytes (TILs), plays a major role in effective tumor cell lysis [9].

Associations of CDH17 with chemical compounds

• LI-Cadherin is a transmembrane glycoprotein involved in cell adhesion of epithelial cells [15].
• In order to obtain sufficiently soluble model compounds, glycan side chains of T-antigen, (2,6)sialyl T-antigen and sialyl TN-antigen structure were linked to the serine located in the supposed turn sequence of the LI-cadherin recognition domain [15].
• TNF-{alpha} increases tyrosine phosphorylation of vascular endothelial cadherin and opens the paracellular pathway through fyn activation in human lung endothelia [16].
• The NF2 encoded protein merlin appears to function as a tumour suppressor gene by controlling cadherin-mediated cell-cell adhesion [17].
• Histamine alters cadherin-mediated sites of endothelial adhesion [18].

Physical interactions of CDH17

• Furthermore, the nm23-H1 (-)/E-cadherin (+) coexpression profile was coupled to decreased E-cadherin immunohistochemical protein detection (grade II) in 21% of the cases examined [19].

Co-localisations of CDH17

• CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach [20].

Regulatory relationships of CDH17

• CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithelium and intestinal metaplasia [21].
• Immunofluorescence cytochemistry assay revealed that the LI-cad was predominantly expressed in cytoplasm of HCC cells, contrary to that of E-cad immunostain at the plasma membrane region [22].

Other interactions of CDH17

• In this study, we show that inappropriate expression of R-cadherin in tumor cells results in decreased expression of endogenous cadherins (cadherin switching) and sustained signaling through Rho GTPases [1].
• Alternative mRNA splicing of liver intestine-cadherin in hepatocellular carcinoma [3].
• In conclusion, overexpression of CDH17 is significantly associated with CDX2 [20].
• High frequency of concomitant nm23-H1 and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas [19].
• In contrast, PTR3 and HPT-1 were widely expressed in the human GIT, with predominant expression in the different regions of the colon [23].

Analytical, diagnostic and therapeutic context of CDH17

• EXPERIMENTAL DESIGN: Reverse transcription-PCR (RT-PCR) and quantitative real-time RT-PCR were used to examine alternative mRNA splicing and mRNA level of LI-cadherin in 50 paired tumor-peritumor tissues of 50 HCC and 8 normal liver specimens [3].
• LI-cadherin mRNA was up-regulated from 2.58-fold to 800-fold in over 80% of HCC samples when compared with normal liver by quantitative PCR [3].
• Association of LI-cadherin splicing with tumor venous infiltration, first-year tumor recurrence, and overall survival after partial hepatectomy were determined [3].
• To determine the extent to which cadherin loci could be affected by allelic losses, we used radiation hybrid mapping to define the chromosomal position of five cadherin genes [24].
• Protein expression level of LI-cadherin was determined by Western blotting and immunohistochemistry [13].

References