Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells
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 (GC). DCLK1 overexpression in a majority of solid cancers correlates with lymph node metastases, advanced disease a...
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Published in | Proteomics (Weinheim) Vol. 21; no. 13-14; pp. e2000098 - n/a |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
Wiley Subscription Services, Inc
01.07.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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 (GC). DCLK1 overexpression in a majority of solid cancers correlates with lymph node metastases, advanced disease and overall poor‐prognosis. In cancer cells, DCLK1 expression has been shown to promote epithelial‐to‐mesenchymal transition (EMT), driving disruption of cell‐cell adhesion, cell migration and invasion. Here, we report that DCLK1 influences small extracellular vesicle (sEV/exosome) biogenesis in a kinase‐dependent manner. sEVs isolated from DCLK1 overexpressing human GC cell line MKN1 (MKN1OE‐sEVs), promote the migration of parental (non‐transfected) MKN1 cells (MKN1PAR). Quantitative proteome analysis of MKN1OE‐sEVs revealed enrichment in migratory and adhesion regulators (STRAP, CORO1B, BCAM, COL3A, CCN1) in comparison to MKN1PAR‐sEVs. Moreover, using DCLK1‐IN‐1, a specific small molecule inhibitor of DCLK1, we reversed the increase in sEV size and concentration in contrast to other EV subtypes, as well as kinase‐dependent cargo selection of proteins involved in EV biogenesis (KTN1, CHMP1A, MYO1G) and migration and adhesion processes (STRAP, CCN1). Our findings highlight a specific role of DCLK1‐kinase dependent cargo selection for sEVs and shed new light on its role as a regulator of signaling in gastric tumorigenesis. |
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Bibliography: | Shoukat Afshar‐Sterle and Alin Rai contributed equally to this study. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1615-9853 1615-9861 |
DOI: | 10.1002/pmic.202000098 |