"Dicing and Splicing" Sphingosine Kinase and Relevance to Cancer

被引：34

作者：

Haddadi, Nahal ^{[1
]}

Lin, Yiguang ^{[1
]}

Simpson, Ann M. ^{[1
]}

Nassif, Najah T. ^{[1
]}

McGowan, Eileen M. ^{[1
]}

机构：

[1] Univ Technol Sydney, Sch Life Sci, Fac Sci, 15 Broadway, Sydney, NSW 2007, Australia

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2017年 / 18卷 / 09期

关键词：

sphingosine kinase (SphK); isozymes; variant isoforms; cancer therapy; sphingosine 1 phosphate (S1P); RESISTANT PROSTATE-CANCER; PROTEIN-COUPLED RECEPTOR; NEGATIVE BREAST-CANCER; LEUKEMIC HL-60 CELLS; LONG NONCODING RNA; IN-VIVO; OVARIAN-CANCER; FUNCTIONAL-CHARACTERIZATION; PROTEASOMAL DEGRADATION; ENDOTHELIAL-CELLS;

D O I：

10.3390/ijms18091891

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Sphingosine kinase (SphK) is a lipid enzyme that maintains cellular lipid homeostasis. Two SphK isozymes, SphK1 and SphK2, are expressed from different chromosomes and several variant isoforms are expressed from each of the isozymes, allowing for the multi-faceted biological diversity of SphK activity. Historically, SphK1 is mainly associated with oncogenicity, however in reality, both SphK1 and SphK2 isozymes possess oncogenic properties and are recognized therapeutic targets. The absence of mutations of SphK in various cancer types has led to the theory that cancer cells develop a dependency on SphK signaling (hyper-SphK signaling) or non-oncogenic addiction. Here we discuss additional theories of SphK cellular mislocation and aberrant dicing and splicing as contributors to cancer cell biology and as key determinants of the success or failure of SphK/S1P (sphingosine 1 phosphate) based therapeutics.

引用

页数：25

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