The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/14/3425 |
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| author | Konstantin Drexler Barbara Schwertner Silke Haerteis Thiha Aung Mark Berneburg Edward K. Geissler Maria E. Mycielska Sebastian Haferkamp |
| author_facet | Konstantin Drexler Barbara Schwertner Silke Haerteis Thiha Aung Mark Berneburg Edward K. Geissler Maria E. Mycielska Sebastian Haferkamp |
| author_sort | Konstantin Drexler |
| collection | DOAJ |
| description | 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<sup>+</sup>-gluconate) blocks this citrate-induced proliferation. Furthermore, the 3D in vivo Chick Chorioallantoic Membrane (CAM) model showed that the application of Na<sup>+</sup>-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. |
| first_indexed | 2024-03-09T03:36:46Z |
| format | Article |
| id | doaj.art-b725e7e20e7c4af0935c68db02c9871d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T03:36:46Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b725e7e20e7c4af0935c68db02c9871d2023-12-03T14:47:39ZengMDPI AGCancers2072-66942022-07-011414342510.3390/cancers14143425The Role of Citrate Homeostasis in Merkel Cell Carcinoma PathogenesisKonstantin Drexler0Barbara Schwertner1Silke Haerteis2Thiha Aung3Mark Berneburg4Edward K. Geissler5Maria E. Mycielska6Sebastian Haferkamp7Department of Dermatology, University Medical Center, 93053 Regensburg, GermanyDepartment of Dermatology, University Medical Center, 93053 Regensburg, GermanyInstitute for Molecular and Cellular Anatomy, University of Regensburg, 93053 Regensburg, GermanyInstitute for Molecular and Cellular Anatomy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Dermatology, University Medical Center, 93053 Regensburg, GermanyDepartment of Surgery, Section of Experimental Surgery, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Structural Biology, Institute of Biophysics and Physical Biochemistry, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, GermanyDepartment of Dermatology, University Medical Center, 93053 Regensburg, GermanyMerkel 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<sup>+</sup>-gluconate) blocks this citrate-induced proliferation. Furthermore, the 3D in vivo Chick Chorioallantoic Membrane (CAM) model showed that the application of Na<sup>+</sup>-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.https://www.mdpi.com/2072-6694/14/14/3425cancerMerkel cell carcinomacitratepmCiCgluconate |
| spellingShingle | Konstantin Drexler Barbara Schwertner Silke Haerteis Thiha Aung Mark Berneburg Edward K. Geissler Maria E. Mycielska Sebastian Haferkamp The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis Cancers cancer Merkel cell carcinoma citrate pmCiC gluconate |
| title | The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis |
| title_full | The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis |
| title_fullStr | The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis |
| title_full_unstemmed | The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis |
| title_short | The Role of Citrate Homeostasis in Merkel Cell Carcinoma Pathogenesis |
| title_sort | role of citrate homeostasis in merkel cell carcinoma pathogenesis |
| topic | cancer Merkel cell carcinoma citrate pmCiC gluconate |
| url | https://www.mdpi.com/2072-6694/14/14/3425 |
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