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The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis
Drexler, Konstantin, Schwertner, Barbara, Haerteis, Silke, Aung, Thiha, Berneburg, Mark, Geissler, Edward K., Mycielska, Maria E.
und Haferkamp, Sebastian
(2022)
The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis.
Cancers 14 (14), S. 3425.
Veröffentlichungsdatum dieses Volltextes: 16 Aug 2022 14:04
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.52750
Zusammenfassung
Simple Summary Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer. Despite important progress, overall understanding of the events that drive MCC carcinogenesis remains incomplete. We discovered that the plasma membrane citrate transporter (pmCiC) is upregulated in Merkel cell carcinoma cell lines. Cancer cells import extracellular citrate via pmCiC to support their ...
Simple Summary Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer. Despite important progress, overall understanding of the events that drive MCC carcinogenesis remains incomplete. We discovered that the plasma membrane citrate transporter (pmCiC) is upregulated in Merkel cell carcinoma cell lines. Cancer cells import extracellular citrate via pmCiC to support their metabolism, which is critical to support proliferation and metastatic spread. In this study, we show that inhibition of pmCiC can decrease the growth rate of Merkel cell carcinoma cell lines. Targeting pmCiC and thereby the tumor metabolism should be considered further as a potential anti-cancer therapy. Merkel cell carcinoma (MCC) is a rare but highly aggressive tumor of the skin with a poor prognosis. The factors driving this cancer must be better understood in order to discover novel targets for more effective therapies. In the search for targets, we followed our interest in citrate as a central and critical metabolite linked to fatty acid synthesis in cancer development. A key to citrate uptake in cancer cells is the high expression of the plasma membrane citrate transporter (pmCiC), which is upregulated in the different adenocarcinoma types tested so far. In this study, we show that the pmCiC is also highly expressed in Merkel cell carcinoma cell lines by western blot and human tissues by immunohistochemistry staining. In the presence of extracellular citrate, MCC cells show an increased proliferation rate in vitro; a specific pmCiC inhibitor (Na+-gluconate) blocks this citrate-induced proliferation. Furthermore, the 3D in vivo Chick Chorioallantoic Membrane (CAM) model showed that the application of Na+-gluconate also decreases Merkel cell carcinoma growth. Based on our results, we conclude that pmCiC and extracellular citrate uptake should be considered further as a potential novel target for the treatment of Merkel cell carcinoma.
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Details
| Dokumentenart | Artikel | ||||
| Titel eines Journals oder einer Zeitschrift | Cancers | ||||
| Verlag: | MDPI | ||||
|---|---|---|---|---|---|
| Ort der Veröffentlichung: | BASEL | ||||
| Band: | 14 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 14 | ||||
| Seitenbereich: | S. 3425 | ||||
| Datum | 14 Juli 2022 | ||||
| Institutionen | Medizin > Lehrstuhl für Chirurgie Medizin > Lehrstuhl für Dermatologie und Venerologie Biologie und Vorklinische Medizin > Institut für Biophysik und physikalische Biochemie Biologie und Vorklinische Medizin > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie | ||||
| Identifikationsnummer |
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| Stichwörter / Keywords | TUMOR ANGIOGENESIS; METABOLISM; cancer; Merkel cell carcinoma; citrate; pmCiC; gluconate | ||||
| Dewey-Dezimal-Klassifikation | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status | Veröffentlicht | ||||
| Begutachtet | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden | Ja | ||||
| URN der UB Regensburg | urn:nbn:de:bvb:355-epub-527500 | ||||
| Dokumenten-ID | 52750 |
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