Acid ceramidase upregulation in prostate cancer: role in tumor development and implications for therapy.
Bioactive sphingolipids, such as ceramide, sphingosine and sphingosine-1-phosphate are known bio-effector molecules which play important roles in various aspects of cancer biology including cell proliferation, growth arrest, apoptosis, metastasis, senescence and inflammation. Therefore, enzymes involved in ceramide metabolism are gaining recognition as being critical regulators of cancer cell growth and/or survival. We previously observed that the ceramide metabolizing enzyme, acid ceramidase (AC) is upregulated in tumor tissues. Studies have now concluded that this creates a dysfunctional ceramide pathway, which is responsible for tumor progression and resistance to chemotherapy and radiation. This suggests that development of small-molecule drugs that inhibit AC enzyme activity is a promising approach for improving standard cancer therapy and patient's clinical outcomes.
Liu
Xiang
X
Medical University of South Carolina (MUSC), Division of Basic Sciences, Department of Biochemistry & Molecular Biology, 173 Ashley Avenue, MSC 504, Charleston, South Carolina 29425-5040, USA.
Cheng
Joseph C
JC
Turner
Lorianne S
LS
Elojeimy
Saeed
S
Beckham
Thomas H
TH
Bielawska
Alicja
A
Keane
Thomas E
TE
Hannun
Yusuf A
YA
Norris
James S
JS
D055573:Acid Ceramidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002518:Ceramides / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008297:Male; D011467:Prostate / Q000201:enzymology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013107:Sphingolipids / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D000970:Antineoplastic Agents; D002518:Ceramides; D013107:Sphingolipids; D055573:Acid Ceramidase