Implication of Ceramide Kinase/C1P in Cancer Development and Progression

Simple Summary There are a number of reports in the scientific literature dealing with the implication of ceramide kinase (CERK) and its product, ceramide 1-phosphate (C1P), in the regulation of cell growth and survival, apoptosis, inflammation, and cell migration/invasion. However, no report has so far compiled or put into context the information related to the implication of the CERK/C1P axis in cancer development and metastasis. Hence, the present review highlights the relevance of CERK and C1P in tumorigenesis and tumor dissemination. Whilst CERK produces intracellular C1P, which can act on intracellular targets directly, C1P can also be secreted into the extracellular milieu and interact with sites (possibly receptors) at the plasma membrane of cells. This action can trigger signaling cascades that may end up modulating the expression of specific genes involved in tumor promotion and dissemination. The biology of CERK/C1P in cancer growth and dissemination is herein discussed in detail. Cancer cells rewire their metabolic programs to favor biological processes that promote cell survival, proliferation, and dissemination. Among this relevant reprogramming, sphingolipid metabolism provides metabolites that can favor or oppose these hallmarks of cancer. The sphingolipid ceramide 1-phosphate (C1P) and the enzyme responsible for its biosynthesis, ceramide kinase (CERK), are well established regulators of cell growth and survival in normal, as well as malignant cells through stress-regulated signaling pathways. This metabolite also promotes cell survival, which has been associated with the feedback regulation of other antitumoral sphingolipids or second messengers. C1P also regulates cancer cell invasion and migration of different types of cancer, including lung, breast, pancreas, prostate, or leukemia cells. More recently, CERK and C1P have been implicated in the control of inflammatory responses. The present review provides an updated view on the important role of CERK/C1P in the regulation of cancer cell growth, survival, and dissemination.

Automated summary

This review highlights the relevance of ceramide kinase (CERK) and ceramide 1-phosphate (C1P) in tumorigenesis and tumor dissemination. C1P, produced by CERK, acts directly on intracellular targets and can also be secreted into extracellular space to interact with sites at the plasma membrane of cells. C1P regulates cancer cell growth, survival, invasion, and migration, and has been implicated in the control of inflammatory responses.