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Cell-type plasticity within a tumor has recently been suggested to cause a bidirectional conversion between tumor-initiating stem cells and nonstem cells triggered by an inflammatory stroma. NF-κB represents a key transcription factor within the inflammatory tumor microenvironment. However, NF-κB's function in tumor-initiating cells has not been examined(More)
IKKbeta-dependent NF-kappaB activation plays a key role in innate immunity and inflammation, and inhibition of IKKbeta has been considered as a likely anti-inflammatory therapy. Surprisingly, however, mice with a targeted IKKbeta deletion in myeloid cells are more susceptible to endotoxin-induced shock than control mice. Increased endotoxin susceptibility(More)
SUMMARY IKKb-dependent NF-kB activation plays a key role in innate immunity and inflammation, and inhibition of IKKb has been considered as a likely anti-inflammatory therapy. Surprisingly, however, mice with a targeted IKKb deletion in myeloid cells are more susceptible to endo-toxin-induced shock than control mice. Increased endotoxin susceptibility is(More)
Constitutive activation of EGFR- and NF-κB-dependent pathways is a hallmark of cancer, yet signalling proteins that connect both oncogenic cascades are poorly characterized. Here we define KIAA1199 as a BCL-3- and p65-dependent gene in transformed keratinocytes. KIAA1199 expression is enhanced on human papillomavirus (HPV) infection and is aberrantly(More)
Tumor initiation in the intestine can rapidly occur from Lgr5(+) crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer stem cells. Here, we show that Elp3, the catalytic subunit of the Elongator complex, is required for Wnt-driven intestinal tumor initiation and(More)
The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis.(More)
The Journal of Experimental Medicine regrets that due to a production error, the original version of this paper included incorrect labels to the right of the blots in Fig. 8 B. The legend remains correct, and the corrected figure appears below. The online HTML and PDF versions of this article have been corrected. The error only remains in the print version.
The Journal of Experimental Medicine regrets that due to a production error, the original version of this paper included incorrect labels to the right of the blots in Fig. 8 B. The legend remains correct, and the corrected figure appears below. The online HTML and PDF versions of this article have been corrected. The error only remains in the print version.
Endosomes have important roles in intracellular signal transduction as a sorting platform. Signaling cascades from TLR engagement to IRF3-dependent gene transcription rely on endosomes, yet the proteins that specifically recruit IRF3-activating molecules to them are poorly defined. We show that adaptor protein containing a pleckstrin-homology domain, a(More)
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