Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells

Suzuki, Motoshi; Cao, Ke; Kato, Seiichi; Komizu, Yuji; Mizutani, Naoki; Tanaka, Kouji; Arima, Chinatsu; Tai, Mei Chee; Yanagisawa, Kiyoshi; Togawa, Norie; Shiraishi, Takahiro; Usami, Noriyasu; Taniguchi, Tetsuo; Fukui, Takayuki; Yokoi, Kohei; Wakahara, Keiko; Hasegawa, Yoshinori; Mizutani, Yukiko; Igarashi, Yasuyuki; Inokuchi, Jin-ichi; Iwaki, Soichiro; Fujii, Satoshi; Satou, Akira; Matsumoto, Yōko; Ueoka, Ryuichi; Tamiya‐Koizumi, Keiko; Murate, Takashi; Nakamura, Mitsuhiro; Kyogashima, Mamoru; Takahashi, Takashi

doi:10.1172/jci133806

Cited by 10 publications

(15 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that CERS6 is overexpressed in breast, head and neck, and lung cancers. 18,20,24 The present study explored the expression of CERS6 in gastric tissues. The results of immunohistochemistry and immunoblotting experiment have revealed that, as in other types of cancer, CERS6 was overexpressed in both GC tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

“…The elevated expression of CERS6 has been found to be due in part to the reduced expression of microRNA-101 in lung cancer tissues. 24 However, the mechanism for the overexpression of CERS6 in GC remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…23 Moreover, CERS6 mRNA and protein have been found to be overexpressed in breast cancer, head and neck cancer, and lung cancers. 18,20,24 Our recent literature review on the relationship between CERS6 and cancer prognosis indicates that only one study, by Suzuki et al, determined that CERS6 is overexpressed in lung cancer tissues and cells and that CERS6 could serve as a prognostic biomarker for lung cancer. 24 The expression of CERS6 in GC, the correlation between CERS6 expression and clinicopathologic parameters, and the importance of CERS6 expression in GC prognosis remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…18,20,24 Our recent literature review on the relationship between CERS6 and cancer prognosis indicates that only one study, by Suzuki et al, determined that CERS6 is overexpressed in lung cancer tissues and cells and that CERS6 could serve as a prognostic biomarker for lung cancer. 24 The expression of CERS6 in GC, the correlation between CERS6 expression and clinicopathologic parameters, and the importance of CERS6 expression in GC prognosis remain unclear. The objective of this research is to study the expression of CERS6 in normal and GC tissues and cell lines, to study the role of CERS6 in GC tumorigenicity, and to evaluate the possibility of CERS6 as a target for GC chemotherapy and also as a prognostic biomarker for GC.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway

Uen

Fang

Lin

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

Although gastric cancer (GC) is one of the most common cancers, knowledge of its development, and carcinogenesis is limited. The present study explored the involvement of ceramide synthase 6 (CERS6) in GC carcinogenesis and prognosis. RT-PCR, immunoblotting, and immunohistochemistry were used to examine the expression of CERS6. Transfection and small hairpin RNA technology were used to investigate the effect of CERS6 manipulation on cell proliferation and spread as well as the underlying mechanism. Moreover, xenograft proliferation was employed to explore the influence of CERS6 on tumor growth in animals. It was found that overexpression of CERS6 was significantly correlated with several clinicopathologic parameters and poor disease-free survival. The overexpression and silencing of CERS6 in GC cells facilitated and suppressed cell proliferation and spread as well as xenograft proliferation, respectively. Mechanistic studies further revealed that CERS6 influenced cell proliferation and spread by regulating cell cycle control and metastasis-related protein through the SOCS2/JAK2/STAT3 signaling pathway. Collectively, this study suggests that CERS6 overexpression could be a useful biomarker for predicting the outcomes of GC patients and that CERS6 targeting represents a potential modality for treating GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway

Uen

Fang

Lin

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…17 Recently, Suzuki et al reported that combined treatment with l-a-dimyristoylphosphatidylcholine liposome and the glucosylceramide synthase inhibitor D-PDMP induced NSCLC cell death associated with ceramide accumulation, and promoted cancer cell apoptosis and tumor regression in murine models. 18 In general, there is still limited information on the lipidomics of ceramide species in NSCLC cells or sphingolipid metabolism targeted therapy for NSCLC. In this study, lipidomics analyses were performed to identify the ceramide signature in NSCLC cell-lines with or without ABC294640 treatment.…”

Section: Introductionmentioning

confidence: 99%

The sphingosine kinase 2 inhibitor ABC294640 displays anti‐non‐small cell lung cancer activities in vitro and in vivo

Dai

Smith

Foroozesh

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) accounts for about 85-90% of lung cancer cases, and is the number one killer among cancers in the United States. The majorities of lung cancer patients do not respond well to conventional chemo- and/or radio-therapeutic regimens, and have a dismal 5-year survival rate of ∼15%. The recent introduction of targeted therapy and immunotherapy gives new hopes to NSCLC patients, but even with these agents, not all patients respond, and responses are rarely complete. Thus, there is still an urgent need to identify new therapeutic targets in NSCLC and develop novel anti-cancer agents. Sphingosine kinase 2 (SphK2) is one of the key enzymes in sphingolipid metabolism. SphK2 expression predicts poor survival in NSCLC patients, and is associated with Gefitinib-resistance. In this study, the anti-NSCLC activities of ABC294640, the only first-in-class orally available inhibitor of SphK2, were explored. The results obtained indicate that ABC294640 treatment causes significant NSCLC cell apoptosis, cell cycle arrest and suppression of tumor growth in vitro and in vivo. Moreover, lipidomics analyses revealed the complete signature of ceramide and dihydro(dh)-ceramide species in the NSCLC cell-lines with or without ABC294640 treatment. These findings indicate that sphingolipid metabolism targeted therapy may be developed as a promising strategy against NSCLC.

show abstract

Lipid metabolism in cancer progression and therapeutic strategies

Zou

Shen

et al. 2020

MedComm

157

113

View full text Add to dashboard Cite

Dysregulated lipid metabolism represents an important metabolic alteration in cancer. Fatty acids, cholesterol, and phospholipid are the three most prevalent lipids that act as energy producers, signaling molecules, and source material for the biogenesis of cell membranes. The enhanced synthesis, storage, and uptake of lipids contribute to cancer progression. The rewiring of lipid metabolism in cancer has been linked to the activation of oncogenic signaling pathways and cross talk with the tumor microenvironment. The resulting activity favors the survival and proliferation of tumor cells in the harsh conditions within the tumor. Lipid metabolism also plays a vital role in tumor immunogenicity via effects on the function of the noncancer cells within the tumor microenvironment, especially immune‐associated cells. Targeting altered lipid metabolism pathways has shown potential as a promising anticancer therapy. Here, we review recent evidence implicating the contribution of lipid metabolic reprogramming in cancer to cancer progression, and discuss the molecular mechanisms underlying lipid metabolism rewiring in cancer, and potential therapeutic strategies directed toward lipid metabolism in cancer. This review sheds new light to fully understanding of the role of lipid metabolic reprogramming in the context of cancer and provides valuable clues on therapeutic strategies targeting lipid metabolism in cancer.

show abstract

Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells

Cited by 10 publications

References 0 publications

Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway

Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway

The sphingosine kinase 2 inhibitor ABC294640 displays anti‐non‐small cell lung cancer activities in vitro and in vivo

Lipid metabolism in cancer progression and therapeutic strategies

Contact Info

Product

Resources

About