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  Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells.

Rappa, G., Mercapide, J., Anzanello, F., Le, T. T., Johlfs, M. G., Fiscus, R. R., et al. (2013). Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells. Experimental Cell Research, 319(6), 810-819.

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 Creators:
Rappa, Germana, Author
Mercapide, Javier, Author
Anzanello, Fabio, Author
Le, Thuc T, Author
Johlfs, Mary G, Author
Fiscus, Ronald R, Author
Wilsch-Bräuninger, Michaela1, Author           
Corbeil, Denis1, Author           
Lorico, Aurelio, Author
Affiliations:
1Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Abstract: Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1-positive structures appeared in three sizes (small, ≤40 nm; intermediates ~40-80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1-containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma.

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 Dates: 2013
 Publication Status: Issued
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 Identifiers: eDoc: 688499
Other: 5711
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Title: Experimental Cell Research
Source Genre: Journal
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Pages: - Volume / Issue: 319 (6) Sequence Number: - Start / End Page: 810 - 819 Identifier: -