Anchorage-dependent Cell Cycle Progression

The concept of anchorage-dependent growth and the close relationship between anchorage independence and tumorigenicity were first appreciated more than a quarter century ago (9, 16, 23, 24). Penman and his coworkers then showed that incubation of cells in the absence of substratum (e.g., tissue culture plastic or purified extracellular matrix protein [ECM]) resulted in an inhibition of mRNA production and protein synthesis (2). These effects became less pronounced with increasing degrees of cell transformation (27). The Folkman laboratory showed that a spread cell shape, rather than adhesion per se, was required for the proliferation of anchorage- dependent cells (8). Like the effects of growth factors, the growth regulatory effects of cell anchorage and cell shape mapped to the G1 phase of the cell cycle. With the recent explosion of information about cell cycle control in general, and cyclin-dependent...