Loss of cell polarity and tissue architecture are characteristics of malignant cancers derived from epithelial tissues. We provide evidence from Drosophila that a group of membrane-associated proteins act in concert to regulate both epithelial structure and cell proliferation. Scribble (Scrib) is a cell junction-localized protein required for polarization of embryonic and, as demonstrated here, imaginal disc and follicular epithelia. We show that the tumor suppressors lethal giant larvae (lgl) and discs-large (dlg) have identical effects on all three epithelia, and that scrib also acts as a tumor suppressor. Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. scrib, dlg, and lgl show strong genetic interactions. Our data indicate that the three tumor suppressors act together in a common pathway to regulate cell polarity and growth control.

https://science.sciencemag.org/content/sci/289/5476/113.full.pdf

Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors.

We have identified recessive overproliferation mutations by screening and examining clones of mutant cells in genetic mosaics of the fruitfly Drosophila melanogaster. This type of screen provides a powerful approach for identifying and studying potential tumor suppressors. One of the identified genes, lats, has been cloned and encodes a putative protein kinase that shares high levels of sequence similarity with three proteins in budding yeast and Neurospora that are involved in regulation of the cell cycle and growth. Mutations in lats cause dramatic overproliferation phenotypes and various developmental defects in both mosaic animals and homozygous mutants.

Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase

Mammalian epithelial tumors lose polarity as they progress toward malignancy, but whether polarity loss might causally contribute to cancer has remained unclear. In Drosophila, mutations in the "neoplastic tumor suppressor genes" (nTSGs) scribble, discs-large, and lethal giant larvae disrupt polarity of epithelia and neuroblasts, and simultaneously induce extensive overproliferation of these cells, which exhibit malignant-like characteristics. Herein I review what is known about the role of the fly nTSGs in controlling cell polarity and cell proliferation. Incorporating data from mammalian studies, I consider how polarity and proliferation can be coupled, and how disruption of polarity could promote cancer.

/pdf/epithelial-polarity-and-proliferation-control-links-from-the-217ol7a66y.pdf

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Peptidoglycans from bacterial cell walls trigger immune responses in insects and mammals. A peptidoglycan recognition protein, PGRP, has been cloned from moths as well as vertebrates and has been s ...

https://www.pnas.org/content/pnas/97/25/13772.full.pdf

A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster.

The ability of cells to divide asymmetrically is essential for generating diverse cell types during development. The past 10 years have seen tremendous progress in our understanding of this important biological process. We have learned that localized phosphorylation events are responsible for the asymmetric segregation of cell fate determinants in mitosis and that centrosomes and microtubules play important parts in this process. The relevance of asymmetric cell division for stem cell biology has added a new dimension to the field, and exciting connections between asymmetric cell division and tumorigenesis have begun to emerge.

/pdf/asymmetric-cell-division-recent-developments-and-their-15sz923s37.pdf

Asymmetric cell division: recent developments and their implications for tumour biology

Malignant neoplasms that develop in 12 recessive-lethal, larval mutants of Drosophila melanogaster are discussed. These mutations affect the adult optic neuroblasts and ganglion-mother cells in the larval brain, the imaginal discs, and the hematopoietic organs. The malignant neoplasms exhibit fast, autonomous growth, loss of the capacity for differentiation, increased mobility and invasiveness, lethality in situ and after transplantation, and histological, fine structural, and karyotypic abnormalities. Intermediate neoplasms are also found. These combine both benign and malignant qualities. They grow in a noninvasive, compact fashion, typical of benign tumors, yet they also exhibit malignant qualities such as fast, autonomous, and lethal growth, loss of differentiation capacity, changes in cellular morphology, and lethal growth after transplantation into wild-type hosts. Thus Drosophila and vertebrate neoplasms show striking similarities.

Malignant neoplasms of genetic origin in Drosophila melanogaster

A new virus-like particle has been found in Drosophila. Thus far it has been detected only in electron micrographs of certain cells capable of division, such as those in larval imaginal disks, cell lines derived from imaginal disks, cells from a genetically controlled brain tumor, and adult gut cells. It appears to be slightly elliptical in shape, about 37 millimicrons by 45 millimicrons, and occurs in both the nucleus and cytoplasm. From the evidence it is suggested that the particle is a new virus.

http://science.sciencemag.org/content/sci/157/3790/810.full.pdf

Virus-like particles in normal and tumorous tissues of Drosophila.

http://science.sciencemag.org/content/sci/158/3800/534.4.full.pdf

Elisabeth Gateff

Papers

Malignant neoplasms of genetic origin in Drosophila melanogaster

Virus-like particles in normal and tumorous tissues of Drosophila.

Control Systems in Insect Development