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Front Cell Dev Biol 2023 Jan 01;11:1271178. doi: 10.3389/fcell.2023.1271178.
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ADAM11 a novel regulator of Wnt and BMP4 signaling in neural crest and cancer.

Pandey A , Cousin H , Horr B , Alfandari D .

Introduction: Cranial neural crest (CNC) cells are induced at the border of the neural plate by a combination of FGF, Wnt, and BMP4 signaling. CNC then migrate ventrally and invade ventral structures where they contribute to craniofacial development. Methods: We used loss and gain of function experiments to determine phenotypes associated with the perturbation of Adam11 expression in Xenopus Laevis. Mass spectrometry to identify partners of Adam11 and changes in protein expression in CNC lacking Adam11. We used mouse B16 melanoma to test the function of Adam11 in cancer cells, and published database analysis to study the expression of ADAM11 in human tumors. Results: Here we show that a non-proteolytic ADAM, Adam11, originally identified as a putative tumor suppressor binds to proteins of the Wnt and BMP4 signaling pathway. Mechanistic studies concerning these non-proteolytic ADAM lack almost entirely. We show that Adam11 positively regulates BMP4 signaling while negatively regulating β-catenin activity. In vivo, we show that Adam11 influences the timing of neural tube closure and the proliferation and migration of CNC. Using both human tumor data and mouse B16 melanoma cells, we further show that ADAM11 levels similarly correlate with Wnt or BMP4 activation levels. Discussion: We propose that ADAM11 preserves naïve cells by maintaining low Sox3 and Snail/Slug levels through stimulation of BMP4 and repression of Wnt signaling, while loss of ADAM11 results in increased Wnt signaling, increased proliferation and early epithelium to mesenchyme transition.

PubMed ID: 37766964
PMC ID: PMC10520719
Article link: Front Cell Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: adam11 bmp4 bmpr1a ccnd1 clstn2 ctnnb1 fn1 fzd6 fzd7 hsp90ab1 itk lrp2 lrp5 lrp6 myc rpn1 smad1 snai2 sox2 sox3 sox8 sox9 vim
GO keywords: neural tube closure [+]
Antibodies: Adam11 Ab1 Cdh2 Ab3 Ctnnb1 Ab 11 Myc Ab3 Rpn1 Ab1 Smad1/5 Ab1 Sox3 Ab3
Morpholinos: adam11 MO1 adam11 MO2

Disease Ontology terms: cancer [+]
Phenotypes: Xla Wt + adam11 + animal cap explant + dissociation (Fig. 8. A. B) [+]

Article Images: [+] show captions
References [+] :
Abbruzzese, ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site. 2016, Pubmed, Xenbase