Scribble at the crossroads

Abstract

Although proteins involved in determining apical-basal cell polarity have been directly linked to tumorigenesis, their precise roles in this process remain unclear. A recent report in BMC Biology clarifies the signaling pathways that control cell polarity, proliferation and apoptosis downstream of the tumor suppressor and apical-basal polarity determinant Scribble.

Figure 1

Complex interplay between oncogenic pathways. Changes in tumor malignancy from hyperplasia to metastatic cancer result from the accumulation of numerous alterations of normal cellular functions. Cell polarity, cell proliferation and apoptosis are key targets of neoplastic mutations. Proteins such as Scribble, aPKC or JNK (see text) can simultaneously participate in several signaling pathways (dotted arrows) controlling these different cell functions. Consequently, changes in their activity are likely to have dramatic effects on tumor progression. In the case of Scribble, mutations lead to loss of cell polarity, to increased cell proliferation and to the induction of pro-apoptotic pathways via a subset of these intertwined signaling cascades (highlighted in red).