Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer
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 an...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8089 |
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| author | Łukasz Szymański Krystyna Lieto Robert Zdanowski Sławomir Lewicki Jean-Pierre Tassan Jacek Z. Kubiak |
| author_facet | Łukasz Szymański Krystyna Lieto Robert Zdanowski Sławomir Lewicki Jean-Pierre Tassan Jacek Z. Kubiak |
| author_sort | Łukasz Szymański |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T04:17:43Z |
| format | Article |
| id | doaj.art-fe08f22d5c7645b8a0c0054bc1230642 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:17:43Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fe08f22d5c7645b8a0c0054bc12306422023-11-17T23:04:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01249808910.3390/ijms24098089Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and CancerŁukasz Szymański0Krystyna Lieto1Robert Zdanowski2Sławomir Lewicki3Jean-Pierre Tassan4Jacek Z. Kubiak5Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Postępu 36A, 05-552 Magdalenka, PolandDepartment of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Postępu 36A, 05-552 Magdalenka, PolandLaboratory of Molecular Oncology and Innovative Therapies, Department of Oncology, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, PolandInstitute of Outcomes Research, Maria Sklodowska—Curie Medical Academy, 03-411 Warsaw, PolandDynamics and Mechanics of Epithelia Group, Institute of Genetics and Development of Rennes (IGDR), CNRS, University Rennes, UMR 6290, 35043 Rennes, FranceLaboratory of Molecular Oncology and Innovative Therapies, Department of Oncology, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, PolandMaternal 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.https://www.mdpi.com/1422-0067/24/9/8089MELKERKp38MAPKJNKp53 |
| spellingShingle | Łukasz Szymański Krystyna Lieto Robert Zdanowski Sławomir Lewicki Jean-Pierre Tassan Jacek Z. Kubiak 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 MELK ERK p38 MAPK JNK p53 |
| title | Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer |
| title_full | Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer |
| title_fullStr | Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer |
| title_full_unstemmed | Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer |
| title_short | Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer |
| title_sort | differential effects of overexpression of wild type and kinase dead melk in fibroblasts and keratinocytes potential implications for skin wound healing and cancer |
| topic | MELK ERK p38 MAPK JNK p53 |
| url | https://www.mdpi.com/1422-0067/24/9/8089 |
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