Disease relevance of FXYD5

• Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis [1].
• Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness: relationship to e-cadherin expression [2].
• Clinical significance of dysadherin expression in gastric cancer patients [3].
• The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs [4].
• Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls [4].

High impact information on FXYD5

• We have named this cell membrane glycoprotein, which down-regulates E-cadherin and promotes metastasis, dysadherin [1].
• Chemokine (C-C motif) ligand 2 mediates the prometastatic effect of dysadherin in human breast cancer cells [5].
• Expression of dysadherin was found to be highest in breast cancer cell lines and tumors that lacked the estrogen receptor (ER) [5].
• Dysadherin, a cancer-associated membrane glycoprotein, down-regulates E-cadherin and promotes cancer metastasis [5].
• This study examined the role of dysadherin in breast cancer progression [5].

Chemical compound and disease context of FXYD5

• In patients with refractory lymphoma, we tested the hypothesis that high-dose chemotherapy (BEAM) without stem cell support followed by a reduced intensity (RIC) allogeneic transplant with fludarabine and 2 Gy TBI 28 days later results in tumor debulking and establishment of a graft vs lymphoma effect, with acceptable toxicity [6].
• Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis [7].

Biological context of FXYD5

• Two-dimensional electrophoretic mobility shift assay: identification and mapping of transcription factor CTCF target sequences within an FXYD5-COX7A1 region of human chromosome 19 [8].
• Identification, genome mapping, and CTCF binding of potential insulators within the FXYD5-COX7A1 locus of human Chromosome 19q13.12 [9].
• CONCLUSION: In pancreatic ductal adenocarcinoma, dysadherin expression seems to reflect tumor aggressiveness and to be a positive marker of poor prognosis when considered both alone and in combination with downregulation of E-cadherin [2].
• Dysadherin was not expressed in non-neoplastic germ cells, neither in CIS/ITGCNU, but it was highly expressed in all types of germ cell tumours, that demonstrated either embryonic phenotype or somatic differentiation, in most terminally differentiated neoplasms, and in all lymphomas [10].
• Here we used a novel two-dimensional electrophoretic mobility shift assay (2D-EMSA) procedure for identification and mapping of 52 PTS within a 563-kb human genome region located between the FXYD5 and TZFP genes [11].

Anatomical context of FXYD5

• Dysadherin: expression and clinical significance in thyroid carcinoma [4].
• RESULTS: Dysadherin was not expressed in normal gastric epithelium [3].
• Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells [4].
• Since dysadherin is not normally expressed in non-neoplastic testis, it is conceivable that it plays a role in the neoplastic transformation of germ cells [10].
• In our analysis, six pancreatic cancer cell lines showed a positive correlation between dysadherin expression and cell motility [12].

Associations of FXYD5 with chemical compounds

• Dysadherin is a cancer-associated cell membrane glycoprotein [4].
• To assess the importance of O-glycosylation in dysadherin function, dysadherin-transfected hepatocarcinoma cells were cultured in a medium containing benzyl-alpha-GalNAc, a modulator of O-glycosylation [13].
• We have compared the outcome of patients treated with conventional myeloablative regimens and CD34(+)-selected cells (CD34(+) group; n=23) with those receiving reduced-intensity conditioning regimens, consisting of fludarabine (150 mg/m(2)) plus an alkylating agent, followed by unmanipulated grafts (RIC group; n=27) [14].
• Bone marrow plasma cells from RIC contained short gamma 1 heavy-chain transcripts in which a VDJ exon related to the VH2 subgroup was directly joined to the hinge exon; plasma cells from THR contained short gamma 1 transcripts with a VDJ exon related to the VH3 subgroup joined to the CH3 exon [15].
• From our aroma extract dilu-tion analyses (AEDA) applied to naturally aged lager beers emerged an old-beer-like odorant at RICP-SIL 5 CB = 1532 and RIFFAP = 2809, with a FD value close to that of trans-2-nonenal (the well-known cardboard off-flavor found in aged beers) [16].

Regulatory relationships of FXYD5

• Recently, we reported the cloning and characterization of dysadherin and showed that it downregulated E-cadherin and promoted metastasis [2].

Other interactions of FXYD5

• A combination of increased dysadherin expression and reduced E-cadherin expression (< 90%) further worsened the prognosis [2].
• However, in malignant rhabdoid tumor, cell growth cycle that is regulated by hSNF5/INI1 gene seems to be critical to lethal biological behavior rather than dysadherin [17].
• We studied the clinicopathological features in 72 cases of epithelioid sarcoma and in six cases of malignant rhabdoid tumor, and also assessed the immunohistochemical expression of dysadherin, E-cadherin and MIB-1 in epithelioid sarcoma and malignant rhabdoid tumor cases [17].

Analytical, diagnostic and therapeutic context of FXYD5

• PATIENTS AND METHODS: We examined dysadherin and E-cadherin expression in 125 surgically resected pancreatic ductal adenocarcinoma patients using immunohistochemistry [2].
• Cell lines established from proximal-type epithelioid sarcoma revealed significantly higher levels of dysadherin mRNA expression, compared with the levels seen in malignant rhabdoid tumor cell lines by real-time quantitative RT-PCR (P = 0.0433) [17].
• OBJECTIVE: To compare T-cell reconstitution in two groups of patients submitted to allogeneic stem cell transplantation (SCT): those receiving reduced-intensity conditioning (RIC, n = 24) and those receiving myeloablative conditioning (MA, n = 27) [18].
• This probably reflects the profound immunosuppression following RIC SCT, together with the incomplete ablation of recipient-derived B cells [19].
• Reduced-intensity conditioning allogeneic HSCT (RIC) has less regimen-related morbidity and mortality than myeloablative allogeneic HSCT (MT) offering allogeneic transplantation to patients otherwise excluded [20].

References