Akt inhibition promotes hexokinase 2 redistribution and glucose uptake in cancer cells.

Hexokinase II (HK2), the enzyme that catalyzes the first committed step of glycolysis, is overexpressed in many cancers, as is the central signaling kinase Akt. Akt activity promotes HK2 association with the mitochondria, as well as glucose uptake by cancer cells. In HeLa cervical cancer cells, Akt inhibitor IV (Ai4) increased nuclear HK2 localization, while in MDA-MB-231 breast cancer cells, Ai4 merely induced cytoplasmic redistribution without increased nuclear accumulation.

Nucleocytoplasmic shuttling of hexokinase II in a cancer cell.

In yeast, the hexokinase type II enzyme (HXKII) translocates to the nucleus in the presence of excess glucose, and participates in glucose repression. However, no evidence has suggested a nuclear function for HXKII in mammalian cells. Herein, we present data showing nuclear localization of HXKII in HeLa cells, both by immunocytochemistry and subcellular fractionation.

Protein kinase A isozyme switching: eliciting differential cAMP signaling and tumor reversion.

The cAMP-dependent protein kinase types I (PKA-I) and II (PKA-II), composed of identical catalytic (C) subunits but distinct regulatory (R) subunits (RI versus RII), are expressed in a balance of cell growth and differentiation. Distortion of this balance may underlie tumorigenesis and tumor growth. Here, we used PC3M prostate carcinoma cells as a model to overexpress wild type and mutant R and C subunit genes and examined the effects of differential expression of these genes on tumor growth.