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Role of Melanoma Inhibitory Activity in Melanocyte Senescence

Role of Melanoma Inhibitory Activity in Melanocyte Senescence

Lena Feuerer, Susanne Lamm, Ingmar Henz, Melanie Kappelmann-Fenzl, Sebastian Haferkamp, Svenja Meierjohann, Claus Hellerbrand, Silke Kuphal, Anja Katrin Bosserhoff

Pigment Cell Melanoma Res. 2019 Nov;32(6):777-791.

PMID: 31172672

Abstract:

The protein melanoma inhibitory activity (MIA) is known to be expressed in melanoma and to support melanoma progression. Interestingly, previous studies also observed the expression of MIA in nevi. Concentrating on these findings, we revealed that MIA expression is correlated with a senescent state in melanocytes. Induction of replicative or oncogene-induced senescence resulted in increased MIA expression in vitro. Notably, MIA knockdown in senescent melanocytes reduced the percentage of senescence-associated beta-Gal-positive cells and enhanced proliferation. Using the melanoma mouse model Tg(Grm1), MIA-deficient mice supported the impact of MIA on senescence by showing a significantly earlier tumor onset compared to controls. In melanocytes, MIA knockdown led to a downregulation of the cell cycle inhibitor p21 in vitro and in vivo. In contrast, after induction of hTERT in human melanoma cells, p21 regulation by MIA was lost. In summary, our data show for the first time that MIA is a regulator of cellular senescence in human and murine melanocytes.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42414469	MIA human			Price

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