Alternative titles; symbols
HGNC Approved Gene Symbol: PCDH7
Cytogenetic location: 4p15.1 Genomic coordinates (GRCh38): 4:30,720,369-31,146,800 (from NCBI)
Members of the cadherin superfamily of proteins are membrane-associated glycoproteins that mediate calcium-dependent cell-cell adhesion. All have an extracellular domain containing repeats of the approximately 110-amino acid cadherin motif, a transmembrane domain, and a relatively small cytoplasmic domain. Protocadherins (Pcdhs), which comprise one class of cadherins, seem to function as cell-cell recognition molecules and as components in a signal transduction pathway. Using a cloning strategy to identify genes whose products are membrane proteins, Yoshida et al. (1998) isolated a partial gastric adenocarcinoma cell line cDNA with homology to the Pcdhs. By analyzing additional cDNAs, they determined that the gene, termed BH-Pcdh or PCDH7, is expressed as 3 isoforms with different cytoplasmic tails. The predicted proteins, designated BH-Pcdh-a, -b, and -c, are 1,069, 1,072, and 1,200 amino acids long, respectively. All 3 isoforms contain 7 cadherin repeats in the extracellular domain. The PCDH7 proteins are most closely related to PCDH1 (603626), with 46 to 49% overall sequence identity. Northern blot analysis revealed that a 9-kb PCDH7 transcript is expressed predominantly in brain and heart and at lower levels in various other tissues. An additional 4.5-kb mRNA was observed in several cancer cell lines. Both transcripts contained the same open reading frame.
Chen et al. (2016) reported that human and mouse breast and lung cancer cells express PCDH7, which promotes the assembly of carcinoma-astrocyte gap junctions composed of connexin-43 (CX43; 121014). Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells use these channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and production of inflammatory cytokines such as interferon-alpha (IFNA; see 147660) and tumor necrosis factor (TNF; 191160). As paracrine signals, these factors activate the STAT1 (600555) and NFKB (see 164011) pathways in brain metastatic cells, thereby supporting tumor growth and chemoresistance. The orally bioavailable modulators of gap junctions meclofenamate and tonabersat break this paracrine loop, and Chen et al. (2016) provided proof of principle that these drugs could be used to treat established brain metastasis.
By analysis of somatic cell hybrid panels, Yoshida et al. (1998) mapped the PCDH7 gene to 4p15.
Chen, Q., Boire, A., Jin, X., Valiente, M., Er, E. E., Lopez-Soto, A., Jacob, L. S., Patwa, R., Shah, H., Xu, K., Cross, J. R., Massague, J. Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature 533: 493-498, 2016. Note: Erratum: Nature 544: 124 only, 2017. [PubMed: 27225120] [Full Text: https://doi.org/10.1038/nature18268]
Yoshida, K., Yoshitomo-Nakagawa, K., Seki, N., Sasaki, M., Sugano, S. Cloning, expression analysis, and chromosomal localization of BH-protocadherin (PCDH7), a novel member of the cadherin superfamily. Genomics 49: 458-461, 1998. [PubMed: 9615233] [Full Text: https://doi.org/10.1006/geno.1998.5271]