Journal ArticleDOI
Ceramide-orchestrated signalling in cancer cells
Samy A.F. Morad,Myles C. Cabot +1 more
TLDR
This Review focuses on ceramide signalling and the targeting of specific metabolic junctures to amplify the tumour suppressive activities of ceramide.Abstract:
One crucial barrier to progress in the treatment of cancer has been the inability to control the balance between cell proliferation and apoptosis: enter ceramide. Discoveries over the past 15 years have elevated this sphingolipid to the lofty position of a regulator of cell fate. Ceramide, it turns out, is a powerful tumour suppressor, potentiating signalling events that drive apoptosis, autophagic responses and cell cycle arrest. However, defects in ceramide generation and metabolism in cancer cells contribute to tumour cell survival and resistance to chemotherapy. This Review focuses on ceramide signalling and the targeting of specific metabolic junctures to amplify the tumour suppressive activities of ceramide. The potential of ceramide-based therapeutics in the treatment of cancer is also discussed.read more
Citations
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Journal ArticleDOI
Prognostic value of glucosylceramide synthase and P-glycoprotein expression in oral cavity cancer.
Ji Won Kim,Yangsoon Park,Jong-Lyel Roh,Kyung-Ja Cho,Seung-Ho Choi,Soon Yuhl Nam,Sang Yoon Kim +6 more
TL;DR: GCS and P-gp expression is associated with poor prognosis, suggesting suitability as novel biomarkers in oral cavity squamous cell carcinoma (OSCC).
Journal ArticleDOI
The yeast model system as a tool towards the understanding of apoptosis regulation by sphingolipids
António Rego,António Rego,Dário Trindade,Dário Trindade,Susana R. Chaves,Stéphen Manon,Vítor Costa,Vítor Costa,Maria João Sousa,Manuela Côrte-Real +9 more
TL;DR: Yeast is undeniably a simple model and it can be anticipated that studies using this model system will further unravel mechanisms underlying the regulation of apoptosis by sphingolipids and contribute to novel therapeutic strategies against serious human diseases associated with dysfunction of sphingoipid-dependent cell death programmes.
Journal ArticleDOI
Targeting glucosylceramide synthase upregulation reverts sorafenib resistance in experimental hepatocellular carcinoma
Milica Stefanovic,Anna Tutusaus,Guillermo A. Martinez-Nieto,Cristina Bárcena,Estefanía de Gregorio,Catia Moutinho,Elisabet Barbero-Camps,Alberto Villanueva,Anna Colell,Montserrat Marí,Carmen García-Ruiz,José C. Fernández-Checa,José C. Fernández-Checa,Albert Morales +13 more
TL;DR: The data reveals that ceramide-modifying enzymes, particularly glucosylceramide synthase (GCS), are upregulated during sorafenib treatment in hepatoma cells (HepG2 and Hep3B), and more importantly, in sorAFenib-resistant cell lines, suggesting that GCS targeting may be a novel strategy to increase sorafinib efficacy in HCC management.
Journal ArticleDOI
Serine-Dependent Sphingolipid Synthesis Is a Metabolic Liability of Aneuploid Cells
Sunyoung Hwang,H. Tobias Gustafsson,Ciara O’Sullivan,Gianna Bisceglia,Xinhe Huang,Christian Klose,Andrej Schevchenko,Robert C. Dickson,Paola Cavaliere,Noah Dephoure,Eduardo M. Torres +10 more
TL;DR: Ceramides and long-chain bases, sphingolipid molecules that slow proliferation and promote survival, are increased by aneuploidy, and remarkably, the fitness of aneuPLoid cells improves or deteriorates upon genetically decreasing or increasing ceramides, respectively.
Journal ArticleDOI
Small molecule schweinfurthins selectively inhibit cancer cell proliferation and mTOR/AKT signaling by interfering with trans-Golgi-network trafficking
Xingfeng Bao,Wanjun Zheng,Naoko Hata Sugi,Kishan Agarwala,Qunli Xu,Zichun Wang,Karen TenDyke,Winnie Lee,Lana Parent,Wei Li,Hongsheng Cheng,Yongchun Shen,Noel Taylor,Zoltan Dezso,Hong Du,Yoshihiko Kotake,Nanding Zhao,John Wang,Maarten H. D. Postema,Mary Woodall-Jappe,Yasutaka Takase,Toshimitsu Uenaka,David G. I. Kingston,Kenichi Nomoto +23 more
TL;DR: A previously unrecognized role of schweinfurthins in regulating trans-Golgi-network trafficking is revealed and this cellular effect with mTOR/AKT signaling and with cancer cell survival and growth is linked.
References
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Journal ArticleDOI
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Journal ArticleDOI
Biologically active sphingolipids in cancer pathogenesis and treatment.
Besim Ogretmen,Yusuf A. Hannun +1 more
TL;DR: This work has shown that ceramide — a central molecule in sphingolipid metabolism — in effect functions as a tumour-suppressor lipid, inducing antiproliferative and apoptotic responses in various cancer cells, and that S1P induces responses that, on aggregate, render S 1P a tumours-promoting lipid.
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