Downregulation of stromal syntenin sustains AML development

Autor: Raphael Leblanc, Rania Ghossoub, Armelle Goubard, Rémy Castellano, Joanna Fares, Luc Camoin, Stephane Audebert, Marielle Balzano, Berna Bou‐Tayeh, Cyril Fauriat, Norbert Vey, Sylvain Garciaz, Jean‐Paul Borg, Yves Collette, Michel Aurrand‐Lions, Guido David, Pascale Zimmermann
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 15, Iss 11, Pp 1-18 (2023)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.202317570
Popis: Abstract The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC). Stromal syntenin deficiency, in turn, generates a pro‐tumoral microenvironment. From serial transplantations in mice and co‐culture experiments, we conclude that syntenin‐deficient BMSC stimulate AML aggressiveness by promoting AML cell survival and protein synthesis. This pro‐tumoral activity is supported by increased expression of endoglin, a classical marker of BMSC, which in trans stimulates AML translational activity. In short, our study reveals a vicious signaling loop potentially at the heart of AML–stroma crosstalk and unsuspected tumor‐suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy.
Databáze: Directory of Open Access Journals
Externí odkaz: