A mouse homologue of the Drosophila tumour-suppressor gene l(2)gl controlled by Hox-C8 in vivo

Tomotsune, Daihachiro; Shoji, Hiromichi; Wakamatsu, Yoshio; Kondoh, Hisato; Takahashi, Nobutaka

doi:10.1038/365069a0

Cited by 96 publications

(68 citation statements)

References 25 publications

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“…The Lgl protein is bound to the inner surface of lateral cell membranes in regions of cell junctions, and it is present in high molecular weight aggregates (Strand et al, 1994a,b). Lgl mouse homolog, Mgl-1, is a possible target for the product of a Hox gene (Tomotsune et al, 1993). Mbt is a prolinerich nuclear protein with a novel zinc ®nger (Wismar et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Mutations in the β-propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain

et al. 2000

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Inactivation of both alleles of the fruit¯y D. melanogaster brain tumor (brat) gene results in the production of a tumor-like neoplasm in the larval brain, and lethality in the larval third instar and pupal stages. We cloned the brat gene from a transposon-tagged allele and identi®ed its gene product. brat encodes for an 1037 amino acid protein with an N-terminal B-box1 zinc ®nger followed by a B-box2 zinc ®nger, a coiled-coil domain, and a C-terminal b-propeller domain with six blades. All these motifs are known to mediate protein ± protein interactions. Sequence analysis of four brat alleles revealed that all of them are mutated at the bpropeller domain. The clustering of mutations in this domain strongly suggests that it has a crucial role in the normal function of Brat, and de®nes a novel protein motif involved in tumor suppression activity. The brat gene is expressed in the embryonic central and peripheral nervous systems including the embryonic brain. In third instar larva brat expression was detected in the larval central nervous system including the brain and the ventral ganglion, in two glands ± the ring gland and the salivary gland, and in parts of the foregut ± the gastric caecae and the proventriculus. A second brat-like gene was found in D. melanogaster, and homologs were identi®ed in the nematode, mouse, rat, and human. Accumulated data suggests that Brat may regulate proliferation and di erentiation by secretion/transportmediated processes.

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Section: Introductionmentioning

confidence: 99%

Mutations in the β-propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain

et al. 2000

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“…In contrast, Scrib has only one human homolog, hScrib, although related proteins include ERBIN, Lano, and Densin-180 (Santoni et al 2002). Lgl has two human homologs, Llgl1 and Llgl2, and a somewhat related protein called Tomosyn is also present (Tomotsune et al 1993;Strand et al 1995;Fujita et al 1998).…”

Section: Do Vertebrate Ntsg Homologs Play a Role In Cancer?mentioning

confidence: 99%

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

Bilder¹

2004

Genes Dev.

511

498

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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.

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“…Homologs of lgl have been identified in many species including man (Hugl-1) and mouse (mgl-1) (Tomotsune et al, 1993;Strand et al, 1995). The tumor suppressor function is conserved between fruit flies and humans since Hugl-1 can rescue Drosophila lgl mutants.…”

Section: Introductionmentioning

confidence: 99%

Expression of Hugl-1 is strongly reduced in malignant melanoma

et al. 2005

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The human gene Hugl-1 (Llgl/Lgl1) has significant homology to the Drosophila tumor suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that is involved in maintaining cell polarity and epithelial integrity. We speculate that Hugl-1 might play a role in epithelialmesenchymal transition (EMT) and that loss of Hugl-1 expression plays a role in the development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of Hugl-1 transcription. We found that Hugl-1 was downregulated or lost in all cell lines and in most of the tumor samples analysed, and that these losses were associated with advanced stage of the disease. Reduced Hugl-1 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Functional assays with stable Hugl-1-transfected cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Further, downregulation of MMP2 and MMP14 (MT1-MMP) and re-expression of E-cadherin was found in the Hugl-1-expressing cell clones supporting a role of Hugl-1 in EMT. Our studies thus indicate that loss of Hugl-1 expression contributes to melanoma progression.

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A mouse homologue of the Drosophila tumour-suppressor gene l(2)gl controlled by Hox-C8 in vivo

Cited by 96 publications

References 25 publications

Mutations in the β-propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain

Mutations in the β-propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain

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

Expression of Hugl-1 is strongly reduced in malignant melanoma

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