Session 8, Abstract 47

RAI14 REGULATES PROLIFERATION/SURVIVAL AND MIGRATION ON FIBRONECTIN SUBSTRATES IN MUTANT KRAS PANCREATIC CANCER CELLS

Julie Hong*, Yvess Adamian, Kishan Bhakta and Malachia Hoover (Jonathan A. Kelber), California State University Northridge, Department of Biology, 18111 Nordhoff Street, Northridge, CA 91330.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States, with less than 7% of patients surviving beyond 5 years. This poor prognosis is due to limited diagnostic tools, therapy refractory tumors and rapid disease progression. We sought to identify new molecular mechanisms that drive progression and therapy resistance in this malignancy. Cross-referencing our list of pseudopodium-enriched (PDE) proteins revealed that RAI14 (Retinoic Acid Induced 14 or Ankycorbin) is upregulated in human pancreatic cancer samples relative to normal pancreas tissue by almost 3-fold. We report here that RAI14 can co-localize with actin stress fibers in PDAC cell lines, consistent with previous reports and RAI14’s unique protein domain structure. We also found no correlation between RAI14 expression and PDAC cell proliferation, migration or resistance/sensitivity to Src kinase inhibitors. We further demonstrate successful RAI14 knockdown at both the RNA and protein levels in wild-type and mutant KRas PDAC cell lines. Interestingly, RAI14 knockdown limits wild-type and mutant KRas PDAC cell migration velocity only on fibronectin substrates. However, RAI14 is necessary for mutant KRas PDAC cell proliferation/survival on both Collagen and Fibronectin. These results correlate with a striking reduction in Src mRNA and protein levels upon RAI14 knockdown in mutant KRas PDAC cells. Results suggest a novel role for RAI14 in the pathology of pancreatic cancer. Future studies will aim to interrogate the extracellular contexts that govern the subcellular localization of RAI14 and how this controls PDAC cell response to standard therapeutic interventions in this malignancy.

 

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