That earlier finding involved the insulin-like growth factor receptor (IGF-1) and a different E3 ligase. "Finding that the epidermal growth factor receptors also ubiquitinate Akt, and that they do so through the Skp2 E3 ligase, was quite unexpected," Lin said.
Finding two paths to ubiquitination implies that there might be more, Lin said.
Regulating cancer's energy engine
Tumor cells evolve to rely mainly on glucose processing to generate energy, grow and thrive. They increase glucose uptake and glycolysis, a process that doesn't involve oxygen and occurs in the cell's cytosol. Non-cancerous cells rely more heavily on oxygen-based metabolism of fatty acids and other nutrients in the cell's mitochondria. This difference is called the Warburg Effect.
In a series of experiments, the researchers blocked Skp2 expression and found:
Poor prognosis, Herceptin resistance
The team analyzed 213 cases of breast cancer treated with modified radical mastectomy but no chemotherapy or radiation. Of these, 80 were HER2-positive. In these tumors Skp2 expression was correlated with:
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center