The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity

Yingying Zhu (1, 2) , Julien Saint-Pol (3, 4) , Viet Nguyen (5, 6) , Eric Rubinstein (7, 6, 8) , Claude Boucheix (5, 6) , Céline Greco (9, 10)

1 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
2 ERL 8228 - Métabolisme et physiologie rénales
3 LBHE - Laboratoire de la Barrière Hémato-Encéphalique
4 UA - Université d'Artois
5 Université Paris-Saclay
6 ONCOSTEM - Modèles de Cellules Souches Malignes et Thérapeutiques
7 CIMI - Centre d'Immunologie et des Maladies Infectieuses
8 Réponses cellulaires au microenvironnement et cancer
9 Modèles de Cellules Souches Malignes et Thérapeutiques
10 Département de Pathologie [CHU Necker]

Tetraspanins are cell surface proteins that induce the compartmentalization of molecules with receptor, signaling, or enzymatic properties in microdomains that could serve the integration of transmembrane signals. Several knockouts illustrate their biological functions such as infertility (CD9/CD81), lymphoma development (CD37), immunological deficiency (CD81), or renal insufficiency (CD151). The link between molecular interactions and organ defects remains often difficult to decipher, as is the relationship between the expression of some tetraspanins and the outcome of tumors. High expression of Tspan8 in tumors is associated with poor prognosis, which may be due to increased cell motility and angiogenesis. In a model of colorectal tumor, we explored Tspan8 interacting molecules by mass spectrometry and found that compared to CD9, Tspan8 specifically recruits the endothelin converting enzyme ECE1 to tetraspanin-enriched microdomains and positively modulates its enzymatic activity. Convergence of Tspan8 and endothelin axis in tumor biology offers a new area of research.

Mots clés: Tspan8 endothelin ECE1 colorectal carcinoma; Tspan8; endothelin; ECE1; colorectal carcinoma

Domaines: Sciences du Vivant [q-bio]

Yingying Zhu, Julien Saint-Pol, Viet Nguyen, Eric Rubinstein, Claude Boucheix, et al.. The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity. Cancers, 2023, 15, ⟨10.3390/cancers15194751⟩. ⟨hal-04247136⟩