GSE121064
Janus kinase 1 plays a critical role in mammary cancer progression
Janus kinases (JAKs) and their downstream STAT proteins play key roles in cytokine  signaling, tissue homeostasis, and cancer development. Using a novel breast cancer  model that conditionally lacks the Janus kinase 1, we show here that JAK1 is essential  for IL-6 class inflammatory cytokine signaling and plays a critical role in metastatic  cancer progression. JAK1 is indispensable for the oncogenic activation of STAT1,  STAT3, and STAT6 in ERBB2-expressing cancer cells, suggesting that ERBB2  receptor tyrosine kinase complexes do not directly activate these STAT proteins in  vivo. A genome-wide gene expression analysis revealed that JAK1 signaling has  pleiotropic effects on several pathways associated with cancer progression. We  established that FOS and MAP3K8 are targets of JAK1/STAT3 signaling that promote  tumorsphere formation and cell migration. The results highlight the significance of  JAK1 as a rational therapeutic target to block IL-6 class cytokines that are master  regulators of cancer-associated inflammation. Overall design: Total RNA was extracted from JAK1 deficient mammary tumor cell lines and wildtype controls expressing JAK1 using the RNeasy Mini Kit (Qiagen).