Dr. Shile Huang's Research Focus

Cell Signaling and Tumorigenesis

mTOR, a serine/threonine kinase, plays a central role in the regulation of proliferation, growth (cell size), differentiation, migration and survival/apoptosis. Rapamycin and its derivatives CCI-779 and RAD001 (designated rapamycins) specifically inhibit the function of mTOR. Tumor cells with dysregulated mTOR signaling are more susceptible than normal cells to rapamycins, suggesting that inhibition of mTOR signaling may be exploited as a potential tumor-selective therapeutic strategy. Despite these findings, the role of mTOR in tumorigenesis and metastasis is poorly characterized. Also, the precise mechanism of antitumor of rapamycin remains obscure. Our laboratory is interested in understanding the function of mTOR in controlling tumor cell survival and migration, and unraveling the action mechanism of rapamycin. We have shown that genetic mutations of p53 sensitize cells to rapamycin.

Under serum free conditions, the response to rapamycin in cells lacking functional p53 is apoptosis. Ectopic expression of p53 or p21Cip1 protects cells from rapamycin-induced apoptosis. Rapamycin induces a cellular stress response characterized by rapid and sustained activation of ASK1 (apoptosis signal-regulating kinase 1) signaling in p53-mutant cells, but only transient in cells expressing functional p53/p21Cip1.