CERS6 required for cell migration and metastasis in lung cancer

Suzuki, Motoshi; Cao, Ke; Kato, Seiichi; Mizutani, Naoki; Tanaka, Kouji; Arima, Chinatsu; Tai, Mei Chee; Nakatani, Norie; Yanagisawa, Kiyoshi; Takeuchi, Toshiyuki; Shi, Hanxiao; Mizutani, Yasuyoshi; Niimi, Atsuko; Taniguchi, Tetsuo; Fukui, Takayuki; Yokoi, Kohei; Wakahara, Keiko; Hasegawa, Yoshinori; Mizutani, Yukiko; Iwaki, Soichiro; Fujii, Satoshi; Satou, Akira; Tamiya‐Koizumi, Keiko; Murate, Takashi; Kyogashima, Mamoru; Tomida, Shuta; Takahashi, Takashi

doi:10.1111/jcmm.15817

Cited by 16 publications

(31 citation statements)

References 31 publications

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“…YBX1, another transcription factor, may also be involved in this pathway. Results of the present in vitro experiments and clinical data analysis, as well as findings in our previous study showing that CERS6 promotes cancer metastasis 4 appear to be consistent with the hypothesis that CEBPγ upregulates cancer metastasis. However, the possibility that CEBPγ has metastasis suppression activity through one or more unidentified pathways cannot be denied.…”

Section: Discussionsupporting

confidence: 92%

“…Findings showing altered expressions of ceramides and CERS family proteins in malignant tumors have been reported 10,12,24,25 . Among CERS family proteins, a high expression level of CERS6 was shown to be associated with metastatic features as well as poor prognosis 4 …”

Section: Resultsmentioning

confidence: 97%

“…Cell migration is associated with the formation of a cell‐structural alteration known as lamellipodia/ruffling (from this point forwards lamellipodia), which is essential for cancer cell metastasis, and induced by PKCζ activation and its complex formation with RAC1 3 . Previously, we proposed that CERS6 expression has effects on cellular ceramide constitution to upregulate the d18:1/16:0 ceramide (C16 ceramide) level, resulting in stimulation of cell migration and invasion activities through RAC1‐positive lamellipodia formation 4 …”

Section: Introductionmentioning

confidence: 99%

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CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation

et al. 2021

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Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y‐box as a cis‐acting element. As a parallel analysis of database records for 149 non–small‐cell lung cancer (NSCLC) cancer patients, we screened for trans‐acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer‐binding protein γ (CEBPγ) or Y‐box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide‐dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y‐box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation

et al. 2021

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“…We speculated that the significant elevation in the level of the Cers in LaC patients could have resulted from the upregulated expression of the enzymes related to the synthesis of ceramide. It was reported that ceramide synthase in a salvage pathway was highly activated in several different tumors, such as human colon cancer ( 24 ), human non-small-cell lung cancer ( 25 ). In vivo , Cer can be also generated by the hydrolysis of SM through the actions of sphingomyelinases.…”

Section: Discussionmentioning

confidence: 99%

Lipidomics Identified Lyso-Phosphatidylcholine and Phosphatidylethanolamine as Potential Biomarkers for Diagnosis of Laryngeal Cancer

Wang

2021

Front. Oncol.

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BackgroundLaryngeal cancer (LaC) remains one of the most common tumors of the respiratory tract with higher incidence in men than in women. The larynx is a small but vital organ on the neck. The dysfunction of the larynx can cause serious health problems such as hoarseness, respiratory distress, and dysphonia. Many lipids (e.g. phospholipid, cholesterol, fatty acid) have been recognized as a crucial role in tumorigenesis. However, the lipid biomarkers are lacking and the lipid molecular pathogenesis of LaC is still unclear.MethodsThis study aims to identify new LaC-related lipid biomarkers used for the diagnosis or early diagnosis of LaC and to uncover their molecular characteristics. Thus, we conducted serum and tissue nontargeted lipidomics study from LaC patients (n = 29) and normal controls (NC) (n = 36) via ultra-high performance liquid chromatography (UHPLC) coupled with high resolution mass spectrometry (HRMS). Multivariate and univariate statistics analyses were used to discriminate LaC patients from NC.ResultsAs expected, a lipid panel including LPC (16:0) and PE (18:0p_20:4) was defined to distinguish the LaC patients from healthy individuals with very high diagnosis performance (area under the curve (AUC) value = 1.000, sensitivity value = 1.000, and specificity value = 1.000). In addition, the levels of Cer, CerG1, SM, PC, PC-O, PE, PI, PS, and ChE in the LaC group significantly increased as compared with the NC group. However, the levels of LPC, LPC-O, LPE, LPE-p, and DG in the LaC group significantly deceased when the one was compared with the NC group. Among significantly changed lipid species, lysophospholipids containing a palmitoyl chain or an arachidonic acid acyl chain remarkably decreased and phospholipids including a palmitoyl chain or an arachidonic acid acyl chain increased in the LaC patients.ConclusionOur results not only indicate that lipidomics is powerful tool to explore abnormal lipid metabolism for the laC, but suggest that lysophospholipids and phospholipids may serve as potential biomarkers for diagnosis of LaC.

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“…Xiaoai Jiedu recipe can inactivate p38 MAPK signaling pathway in NSCLC cells to inhibit its proliferation and metastasis (174). Recent studies have found that CERS6 has important roles in lung cancer migration and metastasis, which proves that the miR-101-CERS6 pathway can be targeted, with potential benefits provided for affected patients (175). High expression of monoamine oxidase A (MAOA) in NSCLC is related to EMT and the development of clinicopathological features of NSCLC (176).…”

Section: New Treatment Strategy and Molecular Mechanisms Of Nsclc Metmentioning

confidence: 99%

Mechanisms and Future of Non-Small Cell Lung Cancer Metastasis

Zhu

Bao²,

Chen

et al. 2020

Front. Oncol.

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Lung cancer, renowned for its fast progression and metastatic potency, is rising to become a leading cause of death globally. It has been long observed that lung cancer is particularly ept in spawning distant metastasis at its early stages, and it can readily colonize virtually any human organ. In recent years, cancer research has shed light on why lung cancer is endowed with its exceptional ability to metastasize. In this review, we will take a comprehensive look at the current research on lung cancer metastasis, including molecular pathways, anatomical features and genetic traits that make lung cancer intrinsically metastatic, as we go from lung cancer’s general metastatic potential to the particular metastasis mechanisms in multiple organs. We highly concerned about the advanced discovery and development of lung cancer metastasis, indicating the importance of lung cancer specific gene mutations, heterogeneity or biomarker discovery, and discussing potential opportunities and challenges. We will also introduce some current treatments that targets certain metastatic strategies of non-small cell lung cancer (NSCLC). Advances made in these regards could be critical to our current knowledge base of lung cancer metastasis.

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CERS6 required for cell migration and metastasis in lung cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 16 publications

References 31 publications

CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation

CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation

Lipidomics Identified Lyso-Phosphatidylcholine and Phosphatidylethanolamine as Potential Biomarkers for Diagnosis of Laryngeal Cancer

Mechanisms and Future of Non-Small Cell Lung Cancer Metastasis

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