Please use this identifier to cite or link to this item: http://hdl.handle.net/10889/11464
Title: Myeloid-derived interleukin-1β drives oncogenic KRAS-NF-κΒ addiction in malignant pleural effusion
Authors: Marazioti, Antonia
Lilis, Ioannis
Vreka, Malamati
Apostolopoulou, Hara
Kalogeropoulou, Argyro
Giopanou, Ioanna
Giotopoulou, Georgia
Krontira, Anthi
Iliopoulou, Marianthi
Kanellakis, Nikolaos
Agalioti, Theodora
Giannou, Anastasios
Jones-Paris, Celestial
Iwakura, Yoichiro
Kardamakis, Dimitrios
Blackwell, Timothy
Taraviras, Stavros
Spella, Magda
Stathopoulos, Georgios
Keywords: Malignant pleural effusion
KRAS mutations
Mutant KRAS facilitates
IKKα-mediated responsiveness
Keywords (translated): Κακοήθης υπεζωκοτική συλλογή
Μεταλλάξεις KRAS
Source: Nature ommunications
Abstract: Malignant pleural effusion (MPE) is a frequent metastatic manifestation of human cancers. While we previously identified KRAS mutations as molecular culprits of MPE formation, the underlying mechanism remained unknown. Here, we determine that non-canonical IKKα-RelB pathway activation of KRAS-mutant tumor cells mediates MPE development and this is fueled by host-provided interleukin IL-1β. Indeed, IKKα is required for the MPE-competence of KRAS-mutant tumor cells by activating non-canonical NF-κB signaling. IL-1β fuels addiction of mutant KRAS to IKKα resulting in increased CXCL1 secretion that fosters MPE-associated inflammation. Importantly, IL-1β-mediated NF-κB induction in KRAS-mutant tumor cells, as well as their resulting MPE-competence, can only be blocked by co-inhibition of both KRAS and IKKα, a strategy that overcomes drug resistance to individual treatments. Hence we show that mutant KRAS facilitates IKKα-mediated responsiveness of tumor cells to host IL-1β, thereby establishing a host-to-tumor signaling circuit that culminates in inflammatory MPE development and drug resistance.
Abstract (translated): -
Appears in Collections:Τμήμα Ιατρικής (Δημοσ. Π.Π. σε περιοδικά)

Files in This Item:
File Description SizeFormat 
nature communic_2.pdf4.56 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons