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.
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Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USAOregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA
Montgomery, Taiowa A.
Carrington, James C.
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Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA
Oregon State Univ, Ctr Genome Res, Corvallis, OR 97331 USA
Oregon State Univ, Mol & Cellular Biol Program, Corvallis, OR 97331 USAOregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA
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Jining Med Univ, Inst Precis Med, Jining 272067, Peoples R ChinaJining Med Univ, Inst Precis Med, Jining 272067, Peoples R China
Bao, Yonghua
Guo, Yongchen
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Jining Med Univ, Inst Precis Med, Jining 272067, Peoples R ChinaJining Med Univ, Inst Precis Med, Jining 272067, Peoples R China
Guo, Yongchen
Zhang, Chenglan
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Hlth Profess Coll Heilongjiang Prov, Dept Nursing, Beian 164000, Peoples R ChinaJining Med Univ, Inst Precis Med, Jining 272067, Peoples R China
Zhang, Chenglan
Fan, Fenghua
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Hlth Profess Coll Heilongjiang Prov, Dept Nursing, Beian 164000, Peoples R ChinaJining Med Univ, Inst Precis Med, Jining 272067, Peoples R China
Fan, Fenghua
Yang, Wancai
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Jining Med Univ, Inst Precis Med, Jining 272067, Peoples R China
Univ Illinois, Dept Pathol, Chicago, IL 60612 USAJining Med Univ, Inst Precis Med, Jining 272067, Peoples R China