Disease relevance of CDH13

• Although defective progenitor-stromal adhesion is a well-recognized feature of chronic myeloid leukemia (CML), the role of CDH13 abnormalities has not been evaluated in this disease [1].
• p16INK4A and CDH13 hypermethylation in tumor and serum of non-small cell lung cancer patients [2].
• Expression of T-cadherin (CDH13, H-Cadherin) in human brain and its characteristics as a negative growth regulator of epidermal growth factor in neuroblastoma cells [3].
• Although functional studies are needed to better define the role of CDH13 and CAV1 in the malignant behavior of osteosarcoma cells, the data presented here provide an aid to understanding the biological functions of L/B/K ALP in bone tumors [4].
• CDH13 protein and mRNA were consistently expressed in all human and murine retinoblastoma compared with normal adult human retina [5].

High impact information on CDH13

• H-cadherin encodes a protein related to the cadherin superfamily of cell adhesion molecules, and its expression is shown to be significantly reduced in human breast carcinoma cell lines and breast cancer specimens [6].
• These studies indicate that downregulation of H-cadherin may be frequent in the breast malignant progression and suggest that it may have prognostic value as a marker for breast cancer development [6].
• Introduction of H-cadherin cDNA markedly diminished tumor cell growth and resulted in a significant change from invasive morphology to a normal cell-like morphology in the Matrigel outgrowth assay [6].
• H-cadherin was localized to chromosome 16q24 and is highly expressed in the heart [6].
• Finally, allele-specific methylation patterns in CDH13 were detected [7].

Biological context of CDH13

• RESULTS: Aberrant de novo methylation of the CDH13 promoter region was observed in 99 (55%) of 179 of CP-CML patients, and 90 of the patients failed to express CDH13 mRNA (P <.0001) [1].
• Nevertheless, absence of CDH13 expression was more frequently observed among Sokal high-risk patients (P =.01) and was also independently associated with a shorter median progression-free survival time (P =.03) and poor cytogenetic response to interferon alfa treatment (P =.0001) [1].
• PURPOSE: Cadherin-13 (CDH13) is a newly characterized cadherin molecule responsible for selective cell recognition and adhesion, the expression of which is decreased by methylation in a variety of human cancers, indicating that the CDH13 gene functions as a tumor suppressor gene [1].
• Loss of heterozygosity at intron 1 of the T-cadherin gene was observed in 8 of 28 informative cases of invasive squamous cell carcinoma [8].
• To explore the molecular mechanism of down-regulation of T-cadherin expression in invasive squamous cell carcinoma, loss of heterozygosity, genetic alternations, and methylation status in the 5' region of the T-cadherin gene were investigated [8].

Anatomical context of CDH13

• Atypical keratinocytes in 27 of 53 specimens of actinic keratosis and 23 of 30 specimens of Bowen's disease expressed T-cadherin [8].
• T-cadherin expression was observed in both normal epidermal basal cells and adnexal epithelial cells of formalin-fixed and paraffin-embedded tissue sections [8].
• We transfected A549 cells (human lung cancer cell line with alveolar type-II cell characteristics) with the T-cadherin expression vector [9].
• Whereas T-cad expression was restricted to endothelial cells (EC) from large blood vessels in normal livers, it was up-regulated in sinusoidal EC from 8/15 invasive HCCs [10].
• HUVECs adherent on T-cad or anti-EC1 substratum exhibited an elongated morphology and associated redistribution of the cytoskeleton and focal adhesions to a distinctly peripheral location [11].

Associations of CDH13 with chemical compounds

• Moreover, 5-aza-2'-deoxycytidine (5-aza-dC) treatment of CDH13-methylated cell lines led to restoration of CDH13 expression [12].
• Using a tetracycline-regulated expression system, we also confirmed that the suppression of cell proliferation was dependent on the expression level of T-cadherin [13].
• The cell adhesion molecule T-cadherin is an unusual member of the cadherin superfamily that lacks a cytoplasmic domain, binding instead to the cell membrane via a glycophosphatidyl inositol anchor [14].
• T-cadherin (T-cad) is a Ca(2+)-dependent cell adhesion glycoprotein bound to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor [15].
• Repression was insensitive to inhibitors of gene transcription (actinomycin D) or de novo protein synthesis (cycloheximide), suggesting AHR/ARNT functions directly in transcriptional repression of T-cad [16].

Co-localisations of CDH13

• T-cadherin and signal-transducing molecules co-localize in caveolin-rich membrane domains of vascular smooth muscle cells [17].

Regulatory relationships of CDH13

• The temporal and spatial expression patterns of T-cadherin and neurite outgrowth-promoting N-cadherin were complementary both in nerve and muscle tissues [18].
• Oxidative stress-induced increases in T-cad were inhibited by the free radical-scavenging antioxidant, N-acetylcysteine, and the flavin-containing oxidase inhibitor, diphenyleneiodonium [19].
• In a double-cell chamber assay, fibroblast growth factor-2 appeared to have a critical role to induce T-cadherin in cultured liver sinusoidal endothelial cells [20].

Other interactions of CDH13

• Promoter methylation of CDH1 and CDH13 were noted in dual SV40- and EBV-infected PBMC, and these two genes were also highly significantly correlated to the presence of SV40 sequences in tumors [21].
• Two genes were consistently overexpressed: OKL38 and CDH13 [22].
• Three genes exhibited higher methylation frequencies in invasive tumors: RASSF1A (30% versus 0%; P = 0.0002), H-cadherin (22% versus 2%; P = 0.013), and APC (22% versus 0%; P = 0.003) [23].
• Finally, we found a significant association of cirrhosis with hypermethylation of the p16INK4a and hypomethylation of the CDH13 genes [24].
• Control vector-transfected A549 cells showed a positive band of SP-D but not of T cadherin [9].

Analytical, diagnostic and therapeutic context of CDH13

• PATIENTS AND METHODS: We examined the methylation status of the CDH13 promoter in 179 chronic phase (CP)-CML patients and in 52 advanced-phase samples and correlated it with mRNA expression using methylation-specific polymerase chain reaction (PCR) and reverse transcriptase PCR [1].
• Western immunoblotting also revealed that mature T-cadherin protein was expressed in cultured human skin tissue equivalent [8].
• Although no structural genomic alternations were found by sequence analysis, aberrant promoter methylation of the T-cadherin gene was found in 12 of 28 invasive squamous cell carcinomas [8].
• Particular relevance for T-cad in cardiovascular tissues is indicated by our present screen (immunoblotting) of human tissues and organs whereby highest expression of T-cad was found in aorta, carotid, iliac and renal arteries and heart [25].
• Confocal microscopy demonstrated that potential signalling functions of T-cadherin at the leading edge are unrelated to physical interactions with caveolin [26].

References