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The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression

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Abstract

Introduction

Ceramide synthases (CERSes) are also known longevity assurance (LASS) genes. CERSes play important roles in the regulation of cancer progression. The CERS family is expressed in a variety of human tumours and is involved in tumorigenesis. They are closely associated with the progression of liver, breast, cervical, ovarian, colorectal, head and neck squamous cell, gastric, lung, prostate, oesophageal, pancreatic and blood cancers. CERSes play diverse and important roles in the regulation of cell survival, proliferation, apoptosis, migration, invasion, and drug resistance. The differential expression of CERSes in tumour and nontumour cells and survival analysis of cancer patients suggest that some CERSes could be used as potential prognostic markers. They are also important potential targets for cancer therapy.

Methods

In this review, we summarize the available evidence on the inhibitory or promotive roles of CERSes in the progression of many cancers. Furthermore, we summarize the identified upstream and downstream molecular mechanisms that may regulate the function of CERSes in cancer settings.

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Abbreviations

4EBP1:

4E-binding protein 1

4NQO:

4-nitroquinoline 1-oxide

ABCB1:

ATP binding cassette subfamily B member 1

AICAR:

Aminoimidazole-4-carboxamide riboside

AMPK:

AMP-activated protein kinase

ASGR1:

Asialoglycoprotein receptor 1

ATF4:

Activating transcription factor 4

Bax:

Bcl-2-associated x

Bcl-2:

B-cell lymphoma 2

BIP:

Binding immunoglobulin protein

cAMP:

Cyclic adenosine monophosphate

Caspase-3:

Cysteinyl aspartate-specific proteinase-3

CDase:

Ceramidase

CDK1:

Cyclin-dependent kinase 1

CERSes:

Ceramide synthases

CHOP:

CEBP-homologous protein

Compound C:

6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-a]-pyrimidine

DISC:

Death-inducing signalling complex

Drp1:

Dynamin-related protein 1

ECM:

Extracellular matrix

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinases

FADD:

Fas-associated protein with death domain

FOXP3:

Forkhead box P3

GBC:

Gallbladder cancer

GCS:

Glucosylceramide synthase

GLUT1:

Glucose transporter type 1

GPER1:

G protein-coupled oestrogen receptor 1

GRP78:

Glucose-regulated protein 78

HCC:

Hepatocellular carcinoma

HDAC1:

Histone deacetylases 1

HK:

Hexokinase

HNSCC:

Head and neck squamous cell carcinoma

HOX:

Homeobox

IκB:

Inhibitory kB

JAK2:

Janus kinase 2

LASS:

Longevity assurance

LC3B-II:

Microtubule-associated protein 1 light chain 3 beta lipidation

MAPK:

Mitogen-activated protein kinase

MCL:

Mantle cell lymphoma

MCT1:

Monocarboxylate transporter 1

MDM2:

Murine double minute 2

MDR:

Multidrug resistant

MFN2:

Mitofusin 2

MRP1:

Multidrug resistance protein 1

NF-κB:

Nuclear factor-κB

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

OSCC:

Oral squamous cell carcinoma

PDAC:

Pancreatic ductal adenocarcinoma

PDT:

Photodynamic therapy

PFK1:

Phosphofructokinase 1

PI3K:

Phosphatidylinositol 3-kinase

PIP4K2C:

Phosphatidylinositol-5-phosphate-4-kinase type-2 gamma

PKB/AKT:

Protein kinase B

PKCζ:

Protein kinase Cζ

p-mTORC:

p-mammalian target of rapamycin complex

RAC1:

Ras-related C3 botulinum toxin substrate 1

R-MA:

R (+)-methanandamide

ROS:

Reactive oxygen species

RT‒qPCR:

Real-time quantitative polymerase chain reaction

S1P:

Sphingosine 1-phosphate

SK1:

Sphingosine kinase 1

SMases:

Sphingomyelinases

SOAT1:

Sterol O-acyltransferase 1

STAT3:

Signal transducer and activator of transcription 3

T-ALL:

T-cell acute lymphoblastic leukaemia

TANK:

TRAF family member associated NF-κB activator

TAZ:

Tafazzin

TLC:

TRAM-LAG1-CLN8

TMSG1:

Tumour metastasis suppressor gene

VEGFA:

Vascular endothelial growth factor A

VM-26:

Teniposide

WT:

Wild-type

XBP1:

X-box binding protein 1

YAP:

Yes-associated protein

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Funding

This work was supported by the National Natural Science Foundation of China (81672731); Xuzhou Municipal Science and Technology Project (KC20106 and KC21209); “333 Project” Award of Jiangsu Province (BRA2020252); Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX21_2580).

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  1. School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, 221116, China

    Mengmeng Zhang, Zhangyun Li, Yuwei Liu, Xiao Ding & Shaohua Fan

  2. Department of Ultrasonic Medicine, The First People’s Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, 221000, China

    Yanyan Wang

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Zhang, M.M. wrote the main manuscript text and prepared the figures. Li, Z.Y., Liu, Y.W. and Ding, X. reviewed the manuscript. Fan, S.H. and Wang, Y.Y. contributed to the conception of the review, and critical revision of the manuscript.

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Zhang, M., Li, Z., Liu, Y. et al. The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression. Cell Oncol. 46, 825–845 (2023). https://doi.org/10.1007/s13402-023-00798-6

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