Unknown

Dataset Information

0

Knocking out alpha-synuclein in melanoma cells downregulates L1CAM and decreases motility.


ABSTRACT: The Parkinson's disease (PD) associated protein, alpha-synuclein (α-syn/SNCA), is highly expressed in aggressive melanomas. The goal of this study was to reveal possible mechanism(s) of α-syn involvement in melanoma pathogenesis. Herein, we asked whether α-syn modulates the expression of the pro-oncogenic adhesion molecules L1CAM and N-cadherin. We used two human melanoma cell lines (SK-MEL-28, SK-MEL-29), SNCA-knockout (KO) clones, and two human SH-SY5Y neuroblastoma cell lines. In the melanoma lines, loss of α-syn expression resulted in significant decreases in the expression of L1CAM and N-cadherin and concomitant significant decreases in motility. On average, there was a 75% reduction in motility in the four SNCA-KOs tested compared to control cells. Strikingly, comparing neuroblastoma SH-SY5Y cells that have no detectable α-syn to SH-SY5Y cells that stably express α-syn (SH/+αS), we found that expressing α-syn increased L1CAM and single-cell motility by 54% and 597%, respectively. The reduction in L1CAM level in SNCA-KO clones was not due to a transcriptional effect, rather we found that L1CAM is more efficiently degraded in the lysosome in SNCA-KO clones than in control cells. We propose that α-syn is pro-survival to melanoma (and possibly neuroblastoma) because it promotes the intracellular trafficking of L1CAM to the plasma membrane.

SUBMITTER: Gajendran N 

PROVIDER: S-EPMC10247798 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Knocking out alpha-synuclein in melanoma cells downregulates L1CAM and decreases motility.

Gajendran Nithya N   Rajasekaran Santhanasabapathy S   Witt Stephan N SN  

Scientific reports 20230607 1


The Parkinson's disease (PD) associated protein, alpha-synuclein (α-syn/SNCA), is highly expressed in aggressive melanomas. The goal of this study was to reveal possible mechanism(s) of α-syn involvement in melanoma pathogenesis. Herein, we asked whether α-syn modulates the expression of the pro-oncogenic adhesion molecules L1CAM and N-cadherin. We used two human melanoma cell lines (SK-MEL-28, SK-MEL-29), SNCA-knockout (KO) clones, and two human SH-SY5Y neuroblastoma cell lines. In the melanoma  ...[more]

Similar Datasets

| S-EPMC7933179 | biostudies-literature
| S-EPMC8269360 | biostudies-literature
| S-EPMC10449643 | biostudies-literature
| S-EPMC6606853 | biostudies-literature
| S-EPMC7596286 | biostudies-literature
| S-EPMC10763032 | biostudies-literature
| S-EPMC8663480 | biostudies-literature
| S-EPMC9027615 | biostudies-literature
| S-EPMC11878343 | biostudies-literature
| S-EPMC2955769 | biostudies-literature