Regulation of CDH19 Expression and Function

Stable Identifier
R-HSA-9764302
DOI
10.3180/R-HSA-9764302.1
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Regulation of CDH19 Expression and Function
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Cadherin-19 (CDH19, also known as CDH7L2) is a classical type II cadherin. The human CDH19 gene is a part of the cadherin gene cluster at the chromosomal bands 18q22-q23, together with CDH7 and CDH20 (Kools et al. 2000). At the plasma membrane, CDH19 associates with alpha-catenin (CTNNA1), beta-catenin (CTNNB1), gamma-catenin (JUP) and delta catenin (CTNND1) (Huang et al. 2022), like other classical type I and type II cadherins. CDH19 possesses five extracellular cadherin domains and, like other classical cadherins, is thought to play a role in the establishment of homotypic cell-cell adhesions during formation of adherens junctions.

In rat, the expression of Cdh19 overlaps with the expression of the neural crest cell marker Sox10 (Takahashi and Osumi 2005). In mouse, it was shown that Sox10 transcription factor, essential for migration of neural crest cells during formation of the enteric nervous system, binds to the Cdh19 gene promoter and stimulates Cdh19 transcription. Cdh19 knockdown results in retarded sacral migration of neural crest cells, while re-expression of Cdh19 partially rescues retarded migration of Sox10-null neural crest cells (Huang et al. 2022). CDH19 is a specific marker of Schwann cell precursors (Takahashi and Osumi 2005, Iribar et al. 2016, Stratton et al. 2017, George et al. 2018, Woods et al. 2021).

During angiogenesis, in response to monocyte chemotactic protein 1 (MCP-1, also known as CCL2 or C-C motif chemokine 2), CDH19 transcription is directly stimulated by ZC3H12A (MCPIP, for MCP-1 induced protein) (Niu et al. 2008, Niu et al. 2013). CDH19 was found to be a target of microRNA miR-197-5p. The circular RNA hsa_circ_006220 was shown to sponge miR-197-5p and lead to upregulation of CDH19 mRNA and protein levels (Shi et al. 2021). Circular RNAs that possess multiple microRNA binding sites act as sponges that, by binding to microRNAs, prevent these microRNAs from associating with their target mRNAs.

Both upregulation and downregulation of CDH19 have been reported in cancer and it has been proposed to play both oncogenic and tumor-suppressive roles, depending on the cancer type. CDH19 mRNA is upregulated in clear-cell sarcoma and correlates with a hypomethylated profile (Dermawan et al. 2022). In glioblastoma, CDH19 is upregulated in cancer stem-like cells (Zorniak et al. 2015). In colorectal tumors, CDH19 is upregulated compared to normal tissue (Bujko et al. 2015). In triple negative breast cancer, CDH19 was proposed to play a tumor suppressor role (Shi et al. 2021). A homozygous deletion of the CDH19 gene was reported in a portion of chondrosarcoma tumor samples (Niini et al. 2012).
Literature References
PubMed ID Title Journal Year
24008336 MCP-1-induced protein promotes endothelial-like and angiogenic properties in human bone marrow monocytic cells

Niu, J, Wang, K, Zhelyabovska, O, Saad, Y, Kolattukudy, PE

J Pharmacol Exp Ther 2013
10995570 Characterization of three novel human cadherin genes (CDH7, CDH19, and CDH20) clustered on chromosome 18q22-q23 and with high homology to chicken cadherin-7

Kools, P, Van Imschoot, G, van Roy, F

Genomics 2000
35347249 Comprehensive genomic profiling of EWSR1/FUS::CREB translocation-associated tumors uncovers prognostically significant recurrent genetic alterations and methylation-transcriptional correlates

Dermawan, JK, Vanoli, F, Herviou, L, Sung, YS, Zhang, L, Singer, S, Tap, WD, Benayed, R, Bale, TA, Benhamida, JK, Dickson, BC, Antonescu, CR

Mod Pathol 2022
26137091 Expression changes of cell-cell adhesion-related genes in colorectal tumors

Bujko, M, Kober, P, Mikula, M, Ligaj, M, Ostrowski, J, Siedlecki, JA

Oncol Lett 2015
28512649 Purification and Characterization of Schwann Cells from Adult Human Skin and Nerve

Stratton, JA, Kumar, R, Sinha, S, Shah, P, Stykel, M, Shapira, Y, Midha, R, Biernaskie, J

eNeuro 2017
29520852 Satellite glial cells represent a population of developmentally arrested Schwann cells

George, D, Ahrens, P, Lambert, S

Glia 2018
23146407 Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative genomic hybridization study

Niini, T, Scheinin, I, Lahti, L, Savola, S, Mertens, F, Hollmén, J, Böhling, T, Kivioja, A, Nord, KH, Knuutila, S

Cancer Genet 2012
25361488 Myelin-forming cell-specific cadherin-19 is a marker for minimally infiltrative glioblastoma stem-like cells

Zorniak, M, Clark, PA, Kuo, JS

J Neurosurg 2015
27303947 Does Schwann cell dedifferentiation originate dermal neurofibromas?

Iribar, H, Jaka, A, Ormaechea, N, Tuneu, A, Izeta, A, Gutiérrez-Rivera, A

Exp Dermatol 2016
33382200 Neurons populating the rectal extrinsic nerves in humans express neuronal and Schwann cell markers

Woods, C, Kapur, RP, Bischoff, A, Lovell, M, Arnold, M, Peña, A, Flockton, A, Sharkey, KA, Belkind-Gerson, J

Neurogastroenterol Motil 2021
15580626 Identification of a novel type II classical cadherin: rat cadherin19 is expressed in the cranial ganglia and Schwann cell precursors during development

Takahashi, M, Osumi, N

Dev Dyn 2005
34532373 CircRNA hsa_circ_0006220 acts as a tumor suppressor gene by regulating miR-197-5p/CDH19 in triple-negative breast cancer

Shi, Y, Han, T, Liu, C

Ann Transl Med 2021
34425092 Direct Interaction of Sox10 With Cadherin-19 Mediates Early Sacral Neural Crest Cell Migration: Implications for Enteric Nervous System Development Defects

Huang, T, Hou, Y, Wang, X, Wang, L, Yi, C, Wang, C, Sun, X, Tam, PKH, Ngai, SM, Sham, MH, Burns, AJ, Chan, WY

Gastroenterology 2022
18364357 Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP)

Niu, J, Azfer, A, Zhelyabovska, O, Fatma, S, Kolattukudy, PE

J Biol Chem 2008
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Authored
Orlic-Milacic, M  (2022-05-25)
Reviewed
Brasch, J  (2023-04-18)
Created
Orlic-Milacic, M  (2022-02-10)
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