| First Author | Cruz VH | Year | 2019 |
| Journal | JCI Insight | Volume | 5 |
| PubMed ID | 30938713 | Mgi Jnum | J:308939 |
| Mgi Id | MGI:6753678 | Doi | 10.1172/jci.insight.126117 |
| Citation | Cruz VH, et al. (2019) Axl-mediated activation of TBK1 drives epithelial plasticity in pancreatic cancer. JCI Insight 5 |
| abstractText | Pancreatic ductal adenocarcinoma (PDA) is characterized by an activating mutation in KRAS. Direct inhibition of KRAS through pharmacological means remains a challenge; however, targeting key KRAS effectors has therapeutic potential. We investigated the contribution of TANK-binding kinase 1 (TBK1), a critical downstream effector of mutant active KRAS, to PDA progression. We report that TBK1 supports the growth and metastasis of KRAS-mutant PDA by driving an epithelial plasticity program in tumor cells that enhances invasive and metastatic capacity. Further, we identify that the receptor tyrosine kinase Axl induces TBK1 activity in a Ras-RalB-dependent manner. These findings demonstrate that TBK1 is central to an Axl-driven epithelial-mesenchymal transition in KRAS-mutant PDA and suggest that interruption of the Axl-TBK1 signaling cascade above or below KRAS has potential therapeutic efficacy in this recalcitrant disease. |
