A core of kinase-regulated interactomes defines the neoplastic MDSC lineage

作者：Gato Canas Maria; Martinez de Morentin Xabier; Blanco Luquin Idoia; Fernandez Irigoyen Joaquin; Zudaire Isabel; Liechtenstein Therese; Arasanz Hugo; Lozano Teresa; Casares Noelia; Chaikuad Apirat; Knapp Stefan; Guerrero Setas David; Escors David^*; Kochan Grazyna; Santamaria Enrique

来源：Oncotarget, 2015, 6(29): 27160-27175.

DOI：10.18632/oncotarget.4746

• MDSC
• proteomics
• interactomes
• kinases
• therapeutic targets

Myeloid-derived suppressor cells (MDSCs) differentiate from bone marrow precursors, expand in cancer-bearing hosts and accelerate tumor progression. MDSCs have become attractive therapeutic targets, as their elimination strongly enhances anti-neoplastic treatments. Here, immature myeloid dendritic cells (DCs), MDSCs modeling tumor-infiltrating subsets or modeling non-cancerous (NC)-MDSCs were compared by in-depth quantitative proteomics. We found that neoplastic MDSCs differentially expressed a core of kinases which controlled lineage-specific (PI3K-AKT and SRC kinases) and cancer-induced (ERK and PKC kinases) protein interaction networks (interactomes). These kinases contributed to some extent to myeloid differentiation. However, only AKT and ERK specifically drove MDSC differentiation from myeloid precursors. Interfering with AKT and ERK with selective small molecule inhibitors or shRNAs selectively hampered MDSC differentiation and viability. Thus, we provide compelling evidence that MDSCs constitute a distinct myeloid lineage distinguished by a "kinase signature" and well-defined interactomes. Our results define new opportunities for the development of anti-cancer treatments targeting these tumor-promoting immune cells.

• 出版日期2015-9-29