CCBIO Seminar – Emily Arner

Speaker: Emily Arner, the Brekken lab, UT Southwestern Medical Center, Texas / Rathmell lab at Vanderbilt University Medical Center, Nashville.

Dr. Emily Arner has received her PhD from UT Southwestern under the mentorship of Dr. Rolf Brekken and is a post-doctoral fellow in the lab of Dr. Kimryn Rathmell at Vanderbilt University Medical Center. Dr. Arner received an F99/K00 pre-doctoral to post-doctoral transition award from NCI.  She is interested in cancer cell plasticity/metastasis and finding novel targets to inhibit this process. 

Title: "AXL-TBK1 driven nuclear AKT3 stabilizes snail/slug to promote EMT"

Time: November 25 at 14.30 (timezone in Norway, 13:30 UK time, 08:30 Boston time, 07:30 Texas time)

Place: Digital event in a Zoom webinar. Link to join Webinar as audience: https://uib.zoom.us/j/61399295455?pwd=a3BHR2VBQUxjOFdLckRZbHpyL3I2UT09

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Host: Jim Lorens

Abstract: Epithelial-to-mesenchymal transition (EMT) contributes to tumor cell survival, immune evasion, migration, invasion, and therapy resistance. Across human cancer, tumors that are high grade, poorly differentiated, and have undergone EMT carry a worse prognosis with a higher likelihood of metastasis. AXL, a receptor tyrosine kinase, drives EMT and is implicated in tumor progression, metastasis, and therapy resistance in multiple cancer types including pancreatic cancer and breast cancer. TANK-binding kinase 1 (TBK1) is central to AXL-driven EMT yet, the mechanism of how TBK1 induces EMT remains unclear. Here, we report that AXL activation stimulates TBK1 binding and phosphorylation of AKT3. TBK1 activation of AKT3 drives binding to slug/snail, protection of snail/slug from proteasomal degradation and translocation of the complex to the nucleus. We show that nuclear translocation of AKT3 is required for AXL-driven EMT and metastasis. Congruently, nuclear AKT3 expression correlates with worse outcome in aggressive breast cancer. These results suggest that AKT3 nuclear activity is an important feature of AXL-driven epithelial plasticity and that selective AKT3 inhibition represents a novel therapeutic avenue for treating aggressive cancer.

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