Oncogenic PI3K mutations lead to NF-κB-dependent cytokine expression following growth factor deprivation.

摘要: The PI3K pathway is one of the most commonly misregulated signaling pathways in human cancers, but its impact on tumor microenvironment has not been considered as deeply autonomous cells. In this study we demonstrate that NF-κB activated by two common mutations, PIK3CA E545K and H1047R. We found markers are strongly upregulated under conditions growth factor deprivation. Gene expression analysis performed cells deprived factors identified repertoire genes altered oncogenic mutations following This gene set closely correlated with signatures from claudin-low basal-like breast tumors, subtypes frequently exhibiting constitutive PI3K/Akt activity. An NF-κB-dependent subset driven was also encoded primarily secreted proteins, suggesting a paracrine role for set. Interestingly, while oncogenes such Ras EGFR leads to cell-autonomous effects, abrogating PI3K-transformed did decrease proliferation or induce apoptosis. However, conditioned media mutant-expressing led increased STAT3 activation recipient THP-1 monocytes normal epithelial IL-6-dependent manner. Together, our findings describe PI3K-driven, transcriptional profile which may play critical promoting amenable progression. These data indicate plays diverse roles downstream different pathways.