AI Article Synopsis
- - Merkel Cell Carcinoma (MCC) is a rare skin cancer influenced by the MCPyV virus, which affects specific genes, particularly NDRG1, crucial for controlling cell growth and movement.
- - The study identified the SET protein, which regulates NDRG1, and found that its expression is heightened in both MCC cells and tumor tissues.
- - Using the inhibitor FTY720 to block the interaction between SET and PP2A led to increased NDRG1 levels and reduced cell proliferation, suggesting that targeting SET could be a potential treatment strategy for MCC.
Article Abstract
Merkel Cell Carcinoma (MCC) is a rare neuroendocrine skin cancer. In our previous work, we decoded genes specifically deregulated by MCPyV early genes as opposed to other polyomaviruses and established functional importance of NDRG1 in inhibiting cellular proliferation and migration in MCC. In the present work, we found the SET protein, (I2PP2A, intrinsic inhibitor of PP2A) upstream of NDRG1 which was modulated by MCPyV early genes, both in hTERT-HK-MCPyV and MCPyV-positive (+) MCC cell lines. Additionally, MCC dermal tumour nodule tissues showed strong SET expression. Inhibition of the SET-PP2A interaction in hTERT-HK-MCPyV using the small molecule inhibitor, FTY720, increased NDRG1 expression and inhibited cell cycle regulators, cyclinD1 and CDK2. SET inhibition by shRNA and FTY720 also decreased cell proliferation and colony formation in MCPyV(+) MCC cells. Overall, these results pave a path for use of drugs targeting SET protein for the treatment of MCC.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552451 | PMC |
| http://dx.doi.org/10.1016/j.virol.2024.110143 | DOI Listing |
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