:
Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to
sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The
intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The
upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic
ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other
end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition,
cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance,
radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and
pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core
objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various
cancer cell lines/models.
S58 Beta-Catenin determines tracheal cell fate and squamous lung cancer progression by modulating intercellular adhesiveness