Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells

Yıl: 2019 Cilt: 6 Sayı: 1a Sayfa Aralığı: 213 - 221 Metin Dili: İngilizce DOI: 10.35193/bseufbd.601582 İndeks Tarihi: 09-01-2020

Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells

Öz:
In the last decade, particular sphingolipids have become renowned for their participation in cellmembrane functions and signaling proceedings that regulate a wide array of cellular manners. Ceramide is amajor molecule of sphingolipids metabolism. It plays vital roles in mediating the major cellular functions suchas cell differentiation, cell-to-cell communication, apoptosis, and proliferation. Recent studies have shown thatceramide metabolism and their metabolic enzymes take important role during migration and cell mobility process.However, the molecular mechanism of sphingolipids involved is unknown. Our efforts in this study, which are servingmechanistically the understanding of ceramide, will be shade some light on this unknown. In this work, particularly,we looked at the effect of ceramide syntheses on migration ability of UM-SCC-22A head and neck squamouscarcinoma cells. Briefly, we identified that alterations in ceramide metabolism by pharmacological inhibitorfumonisin B1, reducing bioactive ceramides, results in activation of the TGF-ß receptor type I and II (TßRI/II) cellsurface localization and, leading to increased cell migration/invasion in UM-SCC-22A head and neck squamouscarcinoma cells. On the other hand, primary cilia length in UM-SCC-22A cells did not changed by decreasedceramide amount. Thus, these data reveal that ceramide synthases/ceramide is a novel factor that regulates TßRI/II tothe primary cilium, controlling cell migration and cancer metastasis.
Anahtar Kelime:

Seramid Metabolizmasının HNSCC Hücrelerinde Primer Silia Uzunluğu ve Tümör Metastazına Etkisi

Öz:
Son on yılda, belirli sfingolipitler, hücre zarı fonksiyonlarına katılımları ve çok çeşitli hücresel davranış sistemini düzenleyen sinyalizasyon işlemleriyle önemli hale gelmiştir. Seramid, sfingolipid metabolizmasının ana molekülüdür. Hücre farklılaşması, hücreden hücreye iletişim, apoptoz ve proliferasyon gibi temel hücresel fonksiyonlara aracılık etmede hayati rol oynar. Son zamanlarda yapılan çalışmalar seramid metabolizmasının ve metabolik enzimlerinin hücre göçü ve hücre mobilitesi sürecinde önemli rol oynadığını göstermiştir. Bununla birlikte, söz konusu sfingolipidlerin moleküler mekanizması bilinmemektedir. Mekanik olarak sistemi anlamaya çalışan bu çalışmadaki verilerimiz bu bilinmeyene ışık tutacaktır. Bu çalışmada, özellikle, seramid sentezlerinin UM-SCC-22A baş ve boyun skuamöz karsinom hücrelerinin göç kabiliyeti üzerindeki etkisine baktık. Kısaca, biyoaktif seramidleri azaltan, farmakolojik inhibitör fumonisin B1 ile seramid metabolizmasındaki değişikliklerin, TGF-ß reseptör tip I ve II (TßRI / II) hücre yüzeyine lokalizasyonunun aktifleşmesine ve hücre göçünün / yayılımının artmasına yol açtığını tespit ettik. Öte yandan, UM-SCC-22A hücrelerinde primer silia uzunluğu, seramid miktarında azalma ile değişmedi. Bu nedenle, bu veriler seramid sentezlerinin / seramidin, TßRI / II'yi primer siliuma taşınımını düzenleyen, hücre göçünü ve kanser metastazını kontrol eden yeni bir faktör olduğunu ortaya koymaktadır.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • Schoenfeld, J. D. (2015). Immunity in head and neck cancer, Cancer immunology research, 3(1), 12-17.
  • Suh, Y., Amelio, I., Urbano, T. G., & Tavassoli, M. (2015). Clinical update on cancer: molecular oncology of head and neck cancer, Cell death & disease, 5(1), e1018.
  • Puram, S. V., & Rocco, J. W. (2015). Molecular aspects of head and neck cancer therapy. Hematology/Oncology Clinics, 29(6), 971-992.
  • Guo, T., & Califano, J. A. (2015). Molecular biology and immunology of head and neck cancer, Surgical Oncology Clinics, 24(3), 397-407.
  • Radisky, D. C., Levy, D. D., Littlepage, L. E., Liu, H., Nelson, C. M., Fata, J. E., & Werb, Z. (2005). Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability, Nature, 436 (7047), 123.
  • Colotta, F., Allavena, P., Sica, A., Garlanda, C., & Mantovani, A. (2009). Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability, Carcinogenesis, 30 (7), 1073-1081.
  • Li, F., & Zhang, N. (2016). Ceramide: therapeutic potential in combination therapy for cancer treatment, Current drug metabolism, 17(1), 37-51.
  • Galadari, S., Rahman, A., Pallichankandy, S., & Thayyullathil, F. (2015). Tumor suppressive functions of ceramide: evidence and mechanisms, Apoptosis, 20(5), 689-711.
  • Dany, M., & Ogretmen, B. (2015). Ceramide induced mitophagy and tumor suppression, Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1853(10), 2834-2845.
  • Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression, Nat Rev Cancer 2:161–174
  • Brodowicz, J., Przegaliński, E., Müller, C. P., & Filip, M. (2017). Ceramide and its related neurochemical networks as targets for some brain disorder therapies, Neurotoxicity research, 1-11.
  • Ogretmen, B. (2018). Sphingolipid metabolism in cancer signalling and therapy, Nature Reviews Cancer, 18(1), 33.
  • Mullen, T. D., Hannun, Y. A., & Obeid, L. M. (2012). Ceramide synthases at the centre of sphingolipid metabolism and biology, Biochemical Journal, 441(3), 789-802.
  • He, Q., Wang, G., Dasgupta, S., Dinkins, M., Zhu, G., & Bieberich, E. (2012). Characterization of an apical ceramide-enriched compartment regulating ciliogenesis, Molecular biology of the cell, 23(16), 3156-3166.
  • Michaud, E. J., & Yoder, B. K. (2006). The primary cilium in cell signaling and cancer, Cancer research, 66(13), 6463-6467.
  • Satir, P., Pedersen, L. B., & Christensen, S. T. (2010). The primary cilium at a glance, J Cell Sci, 123(4), 499-503.
  • Keeling, J., Tsiokas, L., & Maskey, D. (2016). Cellular mechanisms of ciliary length control, Cells, 5(1), 6.
  • He, Q., Wang, G., Wakade, S., Dasgupta, S., Dinkins, M., Kong, J. N., ... & Bieberich, E. (2014). Primary cilia in stem cells and neural progenitors are regulated by neutral sphingomyelinase 2 and ceramide, Molecular biology of the cell, 25(11), 1715-1729.
  • Miyoshi, K., Kasahara, K., Miyazaki, I., & Asanuma, M. (2011). Factors that influence primary cilium length, Acta medica Okayama, 65(5), 279-285.
  • Besschetnova, T. Y., Kolpakova-Hart, E., Guan, Y., Zhou, J., Olsen, B. R., & Shah, J. V. (2010). Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation, Current Biology, 20(2), 182-187.
  • Avasthi, P., & Marshall, W. F. (2012). Stages of ciliogenesis and regulation of ciliary length, Differentiation, 83(2), S30-S42.
  • Park, KM. (2018). Can Tissue Cilia Lengths and Urine Cilia Proteins Be Markers of Kidney Diseases? Chonnam Med J., 54(2): 83–89.
  • Nicholas C. Zitomer, Trevor Mitchell, Kenneth A. Voss, at all. (2009). Ceramide Synthase Inhibition by Fumonisin B1 Causes Accumulation of 1-Deoxysphinganine, J Biol Chem. 284(8): 4786–4795.
  • Alfred H. Merrill Jr., M. Cameron Sullards, Elaine Wang, Kenneth A. Voss, and Ronald T. Riley, (2001). Sphingolipid Metabolism: Roles in Signal Transduction and Disruption by Fumonisins, Environmental Health Perspective, 109 -2
  • Bielawski J., Szulc ZM., Hannun YA, and Bielawska A., (2006). Simultaneous quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry, Methods, 39: 82 – 91.
APA Gencer S (2019). Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. , 213 - 221. 10.35193/bseufbd.601582
Chicago Gencer Salih Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. (2019): 213 - 221. 10.35193/bseufbd.601582
MLA Gencer Salih Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. , 2019, ss.213 - 221. 10.35193/bseufbd.601582
AMA Gencer S Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. . 2019; 213 - 221. 10.35193/bseufbd.601582
Vancouver Gencer S Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. . 2019; 213 - 221. 10.35193/bseufbd.601582
IEEE Gencer S "Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells." , ss.213 - 221, 2019. 10.35193/bseufbd.601582
ISNAD Gencer, Salih. "Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells". (2019), 213-221. https://doi.org/10.35193/bseufbd.601582
APA Gencer S (2019). Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi, 6(1a), 213 - 221. 10.35193/bseufbd.601582
Chicago Gencer Salih Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi 6, no.1a (2019): 213 - 221. 10.35193/bseufbd.601582
MLA Gencer Salih Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi, vol.6, no.1a, 2019, ss.213 - 221. 10.35193/bseufbd.601582
AMA Gencer S Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi. 2019; 6(1a): 213 - 221. 10.35193/bseufbd.601582
Vancouver Gencer S Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi. 2019; 6(1a): 213 - 221. 10.35193/bseufbd.601582
IEEE Gencer S "Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells." Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi, 6, ss.213 - 221, 2019. 10.35193/bseufbd.601582
ISNAD Gencer, Salih. "Impact of the Ceramide Metabolism on Primary Cilia Length and Tumor Metastasis in HNSCC Cells". Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi 6/1a (2019), 213-221. https://doi.org/10.35193/bseufbd.601582