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Colon Cancer: The Role of Sphingolipid Metabolic Enzymes

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Bioactive Sphingolipids in Cancer Biology and Therapy

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Abstract

Colorectal cancer is one of the most common tumors worldwide, with sustained incidence in developed countries and increasing incidence in developing countries. Although recent studies provide knowledge of the molecular signaling pathways that are implicated in colon carcinogenesis, treatments and outcomes still need further improvement. Bioactive sphingolipids, such as ceramide, sphingosine, and sphingosine-1-phosphate (S1P), are signaling molecules that regulate cellular events including cell proliferation, apoptosis, senescence, angiogenesis, and transformation in response to diverse stimuli. Ceramide and sphingosine mediate numerous cell-stress responses, including induction of apoptosis and cell senescence. In contrast, S1P plays pivotal roles in cell survival, migration, and inflammation. These sphingolipids with opposing roles can be quickly metabolized and catabolized within cells, suggesting that the balance between these potent bioactive lipids may dictate cell fate. In this chapter, we review the roles of these bioactive sphingolipids and their metabolic enzymes in colitis, colitis associated cancer, and colorectal cancer.

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Abbreviations

aCDase:

Acid CDase

ACER:

Alkaline CDase

alk-SMase:

Alkaline SMase

AOM:

l Azoxymethane

APC:

Adenomatous polyposis coli

aSMase:

Acid SMase

CAC:

Colitis-associated cancer

CDases:

Ceramidases

CerS:

Ceramide synthases

COX2:

Cyclooxygenase-2

CRC:

Colorectal cancer

DSS:

Dextran sodium sulfate

EGFR:

Epidermal growth factor receptor

FAP:

Familial adenomatous polyposis

IBD:

Inflammatory bowel disease

IL-6:

Interleukin-6

miRNAs:

microRNAs

MMR:

Mismatch repair

MSI:

Microsatellite instability

NaBT:

Sodium butyrate

nCDase:

Neutral CDase

NF-κB:

Nuclear factor kappa B

nSMase:

Neutral SMase

PGE2 :

Prostaglandin E2

PI3K:

Phosphatidylinositol 3-kinase

S1P:

Sphingosine-1-phosphate

S1PR:

S1P receptor

SM:

Sphingomyelins

SMases:

Sphingomyelinases

SphKs:

Sphingosine kinases

SPL:

Sphingosine-1-phosphate lyase

SPPs:

Sphingosine-1-phosphate Phosphatases

STAT3:

Signal transducer and activator of transcription 3

TIMP1:

Tissue inhibitor of metalloproteinase 1

TNBS:

2,4,6-Trinitrobenzenesulfonic acid

TNF-α:

Tumor necrosis factor alpha

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

WT:

Wild type

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Acknowledgement

This work was supported in part by National Institutes of Health grants R01CA124687 (T.K.) R01GM097741 (L.M.O.), P01CA097132 (L.M.O.) and VA MERIT Award (L.M.O.)

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Authors and Affiliations

  1. Cancer Biology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA

    Hideki Furuya & Toshihiko Kawamori

  2. Clinical and Translational Research Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA

    Hideki Furuya

  3. Department of Medicine, Stony Brook University, Stony Brook, NY, 11794, USA

    Songhwa Choi, Lina M. Obeid & Ashley J. Snider

  4. Northport VA Medical Center, Northport, NY, 11768, USA

    Lina M. Obeid & Ashley J. Snider

  5. Department of Pathology, Ihicnimiya Nishi Hospital, 1 Hira, Aza, Kaimei, Ichinomiya, Aichi-Pref., 494-0001, Japan

    Toshihiko Kawamori

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  1. Hideki Furuya
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  2. Songhwa Choi
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  3. Lina M. Obeid
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  4. Toshihiko Kawamori
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  5. Ashley J. Snider
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Correspondence to Ashley J. Snider .

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Editors and Affiliations

  1. Stony Brook University, Stony Brook Cancer Center, Stony Brook, New York, USA

    Yusuf A. Hannun

  2. Dept. of Physiology & Biophysics, Stony Brook University, Stony Brook, New York, USA

    Chiara Luberto

  3. Dept. of Medicine, Stony Brook University, Stony Brook, New York, USA

    Cungui Mao

  4. Dept. of Medicine, Stony Brook University, Stony Brook, New York, USA

    Lina Marie Obeid

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Furuya, H., Choi, S., Obeid, L.M., Kawamori, T., Snider, A.J. (2015). Colon Cancer: The Role of Sphingolipid Metabolic Enzymes. In: Hannun, Y., Luberto, C., Mao, C., Obeid, L. (eds) Bioactive Sphingolipids in Cancer Biology and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-20750-6_7

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