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Drexler, Konstantin ; Schwertner, Barbara ; Haerteis, Silke ; Aung, Thiha ; Berneburg, Mark ; Geissler, Edward K. ; Mycielska, Maria E. ; Haferkamp, Sebastian

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

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftCancers
Verlag:MDPI
Ort der Veröffentlichung:BASEL
Band:14
Nummer des Zeitschriftenheftes oder des Kapitels:14
Seitenbereich:S. 3425
Datum14 Juli 2022
InstitutionenMedizin > 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
WertTyp
10.3390/cancers14143425DOI
Stichwörter / KeywordsTUMOR ANGIOGENESIS; METABOLISM; cancer; Merkel cell carcinoma; citrate; pmCiC; gluconate
Dewey-Dezimal-Klassifikation500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-527500
Dokumenten-ID52750

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