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The Emerging Role of Sphingolipids in Cancer Stem Cell Biology

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Lipidomics of Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Tumours are widely considered to be composed of a heterogeneous population of cells that collectively constitute a “community” that permits tumour cell growth. As a part of this “community”, the influx of invading immune, endothelial, and mesenchymal cells can regulate tumour growth in both positive and negative manners. Even within the tumour cell population itself, there is genetic diversity that divides the overall population into distinct sub-populations. Many chemotherapeutic regimes are effective at targeting the bulk of the tumour population. Despite the apparent eradication of the tumour population, minimal residual disease persists driving disease relapse and the subsequent treatment of relapsed/refractory disease remains a problem. A part of this problem remains the inability of current drug treatment regimens to effectively target the cancer stem cell population. Currently, there is emerging evidence to suggest that sphingolipids and alterations in sphingolipid metabolism contribute to cancer stem cell biology. Here, we summarise these findings and identify potential areas for further investigation.

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Abbreviations

ALDH1:

Aldehyde dehydrogenase 1

AML:

Acute myeloid leukaemia

BCSC:

Breast cancer stem cell

C1P:

Ceramide-1-phosphate

CERT:

Ceramide transport protein

CSC:

Cancer stem cell

EGFR:

Epidermal growth factor receptor

ENL:

Eleven-nineteen-leukaemia

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

FLK-1:

Foetal liver kinase-1

GCS:

Glucosylceramide synthase

HDAC:

Histone deacetylase

HSC:

Haematopoietic stem cell

HSPC:

Haematopoietic stem and progenitor cells

MEF:

Mouse embryonic fibroblast

MLL:

Mixed lineage leukaemia

MSC:

Mesenchymal stem cells

PDGF:

Platelet-derived growth factor

ROS:

Reactive oxygen species

S1P:

Sphingosine 1-phosphate

S1P1–5 :

S1P receptors 1–5

SK:

Sphingosine kinase

TMZ:

Temozolomide

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Acknowledgements

This work was supported by the Fay Fuller Foundation, Neurosurgical Research Foundation, Cancer Council SA Beat Cancer Project Grant (1086295), an Australian Postgraduate Award and Royal Adelaide Hospital Dawes Top-up scholarship to ACL, and a National Health and Medical Research Council of Australia Senior Research Fellowship to SMP.

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  1. Centre for Cancer Biology, University of South Australia and SA Pathology, Frome Road, Adelaide, SA, 5000, Australia

    Alexander C. Lewis, Jason A. Powell & Stuart M. Pitson

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  1. Alexander C. Lewis
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  2. Jason A. Powell
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Correspondence to Stuart M. Pitson .

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  1. The University of Melbourne & Centre for Eye Research Australia, Melbourne, Victoria, Australia

    Alice Pébay

  2. The University of Melbourne & Centre for Eye Research Australia, Melbourne, Victoria, Australia

    Raymond C.B. Wong

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Lewis, A.C., Powell, J.A., Pitson, S.M. (2017). The Emerging Role of Sphingolipids in Cancer Stem Cell Biology. In: Pébay, A., Wong, R. (eds) Lipidomics of Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-49343-5_8

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