Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer - Université de Rennes Accéder directement au contenu
Article Dans Une Revue International Journal of Molecular Sciences Année : 2023

Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer

Résumé

Maternal embryonic leucine-zipper kinase (MELK) plays a significant role in cell cycle progression, mitosis, cell migration, cell renewal, gene expression, embryogenesis, proliferation, apoptosis, and spliceosome assembly. In addition, MELK is known to be overexpressed in multiple types of cancer and is associated with cancer proliferation. Tumorigenesis shares many similarities with wound healing, in which the rate of cell proliferation is a critical factor. Therefore, this study aimed to determine the involvement of MELK in the regulation of cell division in two cell types involved in this process, namely fibroblasts and keratinocytes. We examined how temporal overexpression of wild-type and kinase-dead MELK kinase variants affect the rate of proliferation, viability, cell cycle, and phosphorylation state of other kinases involved in these processes, such as ERK1/2, AKT1, MAPK9, p38, and p53. We explored if MELK could be used as a therapeutic stimulator of accelerated wound healing via increased proliferation. We observed that aberrant expression of MELK results in abnormal proliferation, altered cell cycle distribution, and decreased viability of the cells, which challenge the utility of MELK in accelerated wound healing. Our results indicate that, at least in healthy cells, any deviation from precisely controlled MELK expression is harmful to fibroblasts and keratinocytes.
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hal-04100238 , version 1 (17-05-2023)

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Łukasz Szymański, Krystyna Lieto, Robert Zdanowski, Sławomir Lewicki, Jean-Pierre Tassan, et al.. Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer. International Journal of Molecular Sciences, 2023, 24 (9), pp.8089. ⟨10.3390/ijms24098089⟩. ⟨hal-04100238⟩
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