SNAI2 and TBX3 repress CDH1 gene expression during melanocyte development

Stable Identifier
R-HSA-9825774
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, plasma membrane
ReviewStatus
5/5
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SNAI2 and TBX3 repress CDH1 gene expression during melanocyte development
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Changes in relative levels of E- and N-cadherin contribute to migration of neural crest cells during melanocyte differentiation, and also play a role during the development of melanoma (Li et al, 2001; Gupta et al, 2005; LaBonne et al, 2000; reviewed in Mort et al, 2015).
CDH1, the gene encoding E-cadherin, is downregulated during melanocyte development to allow epithelial-to-mesenchymal transition and associated cell migration to occur (Cano et al, 2000; reviewed in White and Zon, 2008). Signaling through endothelin receptor B (ENDRB) also contributes to the migration of melanocyte precursors by downregulating expression of CDH1 and upregulating expression of CDH2 encoding N-cadherin (Bagnato et al, 2004).
CDH1 expression is repressed by binding of SNAI2, also known as SLUG or SNAIL2, to E-boxes in the promoter, as demonstrated in by EMSA and ChIP in MDCK and in synovial sarcoma cell lines (Hayashida et al, 2006; Saito et al, 2006), In human breast cancer cell lines, overexpression of SNAI2 represses transcription of endogenous CDH1 gene (Hajra et al. 2002).
TBX3 is a member of the T-box transcription factor family of proteins that are involved in establishing and maintaining cell identity (Niu et al, 2021). TBX3 binds to the promoter of the CDH1 gene to repress its expression as demonstrated by EMSA, ChIP and reporter gene assay (Rodriguez et al, 2008).

Literature References
PubMed ID Title Journal Year
16142232 The melanocyte differentiation program predisposes to metastasis after neoplastic transformation

Gupta, PB, Kuperwasser, C, Brunet, JP, Ramaswamy, S, Kuo, WL, Gray, JW, Naber, SP, Weinberg, RA

Nat Genet 2005
14973117 Endothelin B receptor blockade inhibits dynamics of cell interactions and communications in melanoma cell progression

Bagnato, A, Rosanò, L, Spinella, F, Di Castro, V, Tecce, R, Natali, PG

Cancer Res 2004
16943193 Calreticulin represses E-cadherin gene expression in Madin-Darby canine kidney cells via Slug

Hayashida, Y, Urata, Y, Muroi, E, Kono, T, Miyata, Y, Nomata, K, Kanetake, H, Kondo, T, Ihara, Y

J Biol Chem 2006
34897787 Role of T-box genes in cancer, epithelial-mesenchymal transition, and cancer stem cells

Niu, G, Hao, J, Sheng, S, Wen, F

J Cell Biochem 2022
16849535 SYT-SSX1 and SYT-SSX2 interfere with repression of E-cadherin by snail and slug: a potential mechanism for aberrant mesenchymal to epithelial transition in human synovial sarcoma

Saito, T, Nagai, M, Ladanyi, M

Cancer Res 2006
11912130 The SLUG zinc-finger protein represses E-cadherin in breast cancer

Hajra, KM, Chen, DY, Fearon, ER

Cancer Res 2002
18829543 Tbx3 represses E-cadherin expression and enhances melanoma invasiveness

Rodriguez, M, Aladowicz, E, Lanfrancone, L, Goding, CR

Cancer Res 2008
11325858 N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells

Li, G, Satyamoorthy, K, Herlyn, M

Cancer Res 2001
18786412 Melanocytes in development, regeneration, and cancer

White, RM, Zon, LI

Cell Stem Cell 2008
10772801 Snail-related transcriptional repressors are required in Xenopus for both the induction of the neural crest and its subsequent migration

LaBonne, C, Bronner-Fraser, M

Dev Biol 2000
10655586 The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression

Cano, A, Pérez-Moreno, MA, Rodrigo, I, Locascio, A, Blanco, MJ, del Barrio, MG, Portillo, F, Nieto, MA

Nat Cell Biol 2000
25670789 The melanocyte lineage in development and disease

Mort, RL, Jackson, IJ, Patton, EE

Development 2015
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
EDN1, EDN3:EDNRB [plasma membrane] (Homo sapiens)
Regulator
p-S742 TBX3:CDH1 gene [nucleoplasm] (Homo sapiens)
Active Unit
p-S742 TBX3 [nucleoplasm]
Regulator
SNAI2:CDH1 gene [nucleoplasm] (Homo sapiens)
Active Unit
SNAI2 [nucleoplasm]
Authored
Rothfels, K  (2023-01-26)
Reviewed
de la Serna, IL  (2024-05-21)
Vu, HN  (2024-11-05)
Steingrímsson, E  (2024-11-05)
Created
Rothfels, K  (2023-01-26)
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