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PMID:23093405
| Citation |
'Ritterson Lew, C and Tolan, DR (2012) TARGETING OF SEVERAL GLYCOLYTIC ENZYMES USING RNAi REVEALS ALDOLASE AFFECTS CANCER-CELL PROLIFERATION THROUGH A NON-GLYCOLYTIC MECHANISM. J. Biol. Chem. ' |
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| Abstract |
In cancer, glucose uptake and glycolysis are increased regardless of the oxygen concentration in the cell, a phenomenon known as the Warburg effect. Several (but not all) glycolytic enzymes have been investigated as potential therapeutic targets for cancer treatment using RNAi. Here, four previously untargeted glycolytic enzymes - aldolase A, glyceraldehyde 3-phosphate dehydrogenase, triose phosphate isomerase, and enolase 1 - are targeted using RNAi in Ras-transformed NIH-3T3 cells. Of these enzymes, knockdown of aldolase causes the greatest effect, inhibiting cell proliferation by 90%. This defect is rescued by expression of exogenous aldolase. However, aldolase knockdown does not affect glycolytic flux or intracellular ATP concentration, indicating a non-metabolic cause for the cell proliferation defect. Furthermore, this defect could be rescued with an enzymatically-dead aldolase variant that retains the known F-actin binding ability of aldolase. One possible model for how aldolase knockdown may inhibit transformed cell proliferation is through its disruption of actin-cytoskeleton dynamics in cell division. Consistent with this hypothesis, aldolase knockdown cells show increased multinucleation. These results are compared to other studies targeting glycolytic enzymes with RNAi in the context of cancer-cell proliferation, and suggest that aldolase may be a useful target in the treatment of cancer. |
| Links |
PubMed Online version:10.1074/jbc.M112.405969 |
| Keywords |
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| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0004332: fructose-bisphosphate aldolase activity |
ECO:0000314: |
F |
Figure 2 shows the effect of aldolase activity depletion on proliferation of certain cell lines. |
complete | ||||
| GO:0004332: fructose-bisphosphate aldolase activity |
ECO:0000314: |
F |
Figure 2A shows that rat cell lines that are transfected with Aldolase A siRNA have lower aldolase activity. The activity assay is described in reference 17, in which they use fructose bisphosphate as the substrate. This shows fructose bisphosphate aldolase activity. |
complete | ||||
See also
References
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