Sphingolipids including
glycosphingolipids have myriad effects on cell functions and affect
cancer in aspects of
tumorigenesis,
metastasis and
tumor response to treatments. Bioactive ones like
ceramide,
sphingosine 1-phosphate and
globotriaosylceramide initiate and process cellular signaling to alter cell behaviors immediately responding to oncogenic stress or treatment challenges. Recent studies pinpoint that
sphingolipid-mediated gene expression has long and profound impacts on
cancer cells, and these play crucial roles in
tumor progression and in treatment outcome. More than 10
sphingolipids and
glycosphingolipids selectively mediate expressions of approximately 50 genes including c-myc, p21, c-fos,
telomerase reverse transcriptase,
caspase-9, Bcl-x,
cyclooxygenase-2,
matrix metalloproteinases,
integrins, Oct-4,
glucosylceramide synthase and multidrug-resistant gene 1. By diverse functions of these genes,
sphingolipids enduringly affect cellular processes of mitosis, apoptosis, migration, stemness of cancer stem cells and cellular resistance to
therapies. Mechanistic studies indicate that
sphingolipids regulate particular gene expression by modulating phosphorylation and acetylation of
proteins that serve as
transcription factors (β-catenin, Sp1), repressor of transcription (
histone H3), and regulators (SRp30a) in RNA splicing. Disclosing molecular mechanisms by which
sphingolipids selectively regulate particular gene expression, instead of other relevant ones, requires understanding of the exact roles of individual
lipid instead of a group, the signaling pathways that are implicated in and interaction with
proteins or other
lipids in details. These studies not only expand our knowledge of
sphingolipids, but can also suggest novel targets for
cancer treatments.