Growth properties of colonic tumor cells are a function of the intrinsic mitochondrial membrane potential

Development of malignant transformation in the colonic mucosa includes disruption in the equilibrium between proliferation and apoptosis, decreased expression and deletions of the mitochondrial genome, alterations in mitochondrial enzymatic activity, and elevations in the mitochondrial membrane potential (Δφm). Focusing on the role of the Δφm in tumor development and progression, we generated novel isogenic colonic carcinoma cell lines that exhibit highly significant, stable differences in their intrinsic Δφm. Using these cell lines, we have recently shown that the intrinsic Δφm has a significant influence on steady state mitochondrial activity and the extent to which cells enter butyrate-mediated growth arrest and apoptotic cascades. Here, we report that the Δφm is also profoundly linked to important tumorigenic properties of the cells. Compared with cells with lower Δφm, cells with elevated intrinsic Δφm have an enhanced capacity to (a) respond to hypoxia by avoiding apoptosis and initiating angiogenesis, (b) escape anoikis and grow under anchorage-independent conditions, and (c) invade the basement membrane. Combined with our previous work, these data implicate the intrinsic Δφm of colonic carcinoma cells in determining the probability of tumor expansion and progression.