A model of epithelial cancer has been developed using the loss-of-function mutations of the Drosophila scrib gene in combination with a constitutively active form of the Drosophila Raf gene, assayed in the developing eye. See also the human disease model reports 'cancer, epithelial, SCRIB-related' (FBhh0000587), 'cancer, multiple, RAF1-related' (FBhh0000558), and 'cancer, epithelial, RAS-SCRIB-related' (FBhh0000585).
When induced in the developing eye during the larval stage, scrib(-) clones result in small benign lesions in the adult eye that appear undifferentiated and disorganized. Clones induced in the developing eye that express activated Raf (RafUAS.F179) develop into vigorously proliferating tissue during larval stages and ultimately overgrow much of the adult eye. This tissue overgrowth remains restricted to the tissues derived from the eye-antennal disc and is apparently not invasive; the animals survive until pharate adult stages. When clones containing the activated Raf allele combined with a loss-of-function mutation for scrib are induced, massive and invasive overgrowth occurs in larval stages, which kills the animal before pupation. Combining an additional element, an activated form of hep which results in increased JNK signaling, significantly, but not completely, suppresses the aggressive overgrowth.
This disease model has been used to investigate the disruption of zinc homeostasis that has been observed for various cancers.
[updated Apr. 2021 by FlyBase; FBrf0222196]
Ortholog of human SCRIB and LRRC1 (1 Drosophila to 2 human); Dmel\scrib shares 33% identity and 45% similarity with the human SCRIB gene. The human LRRC1 gene encodes a much smaller protein, corresponding to the amino end of SCRIB and Dmel\scrib; it shares 57% identity and 73% similarity with Dmel\scrib within that extent.
High-scoring ortholog of human RAF1, BRAF, and ARAF (1 Drosophila to 3 human); Dmel\Raf shares 43-47% identity and 56-60% similarity with the human genes.