Poster Presentation 26th Annual Lorne Proteomics Symposium 2021

The cancer stem cell marker DCLK1 influences extracellular vesicle biogenesis and cargo-selection in a kinase dependent manner promoting migration and adhesion processes in gastric cancer. (#115)

Annalisa Carli 1 2 , Shoukat Sterle 2 , Alin Rai 3 , Fleur M Ferguson 4 5 , Nathanael S Grey 4 5 , Matthias Ernst 1 2 , David W Greening 1 3 , Michael Buchert 1 2
  1. La Trobe University, Heidelberg, VIC, Australia
  2. Cancer and Inflammation Program, Olivia Newton-John Cancer Research Institute, HEIDELBERG, VIC, Australia
  3. The Baker Institute, Melbourne, VIC, Australia
  4. Department of Cancer Biology, Dana-Faber Cancer Institute, Boston, MA, USA
  5. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

Doublecortin-like kinase 1 (DCLK1) is a putative cancer stem cell marker, a promising diagnostic and prognostic maker for malignant tumors and a proposed driver gene for gastric cancer. The overexpression of DCLK1 correlates with advanced disease and overall poor-prognosis. In cancer cells, DCLK1 expression has been shown to promote an epithelial-to-mesenchymal transition (EMT), loss of cell-cell adhesion, and promoting cell migration and invasion.  Here, we report that DCLK1 influences extracellular vesicle (EV) biogenesis in a kinase-dependent manner and EVs originating from DCLK1 overexpressing MKN1 (MKN1OE) gastric cancer cells can induce cell migration of parental isogenic cells (MKN1PAR). The quantitative proteomics analysis of MKN1OE-sEVs revealed enrichment in migratory and adhesion processes. Moreover, using a specific small molecule inhibitor of DCLK1, we reversed the observed increase in EV size and concentration, as well as kinase dependent cargo selection of proteins involved in EV biogenesis and migration and adhesion processes. Our findings highlight a specific role of DCLK1-kinase dependent cargo selection for EVs and shed new light on its role as a regulator of signaling in gastric tumorigenesis.