Human Disease Model Report: cancer, epithelial, Toll-receptor-related

General Information

Name

cancer, epithelial, Toll-receptor-related

FlyBase ID

FBhh0001440

Disease Ontology Term

carcinoma

Parent Disease

OMIM

Overview

Drosophila cancer models 'cancer, epithelial, RAS-SCRIB-related' (FBhh0000585) and 'cancer, epithelial, RAS-LLGL-related' (FBhh0000588) have been used in genetic screens for modulators of tumor growth and invasion. Mutations of two Drosophila Toll receptors, Toll-6 and Toll-7, have been identified in these screens.

Knockdown of Dmel\Toll-6, effected by RNAi and using the RAS-SCRIB model, has minimal effect upon tumor growth but dramatically reduces tumor invasion rate.

Knockdown of Dmel\Toll-7, effected by RNAi and using the RAS-LLGL model, inhibits both tumor growth and tumor invasion rate. Assaying the effect of Toll-7 alone, expression of a constitutively active form of Toll-7 in the wing disc results in tissue overgrowth and a small amount invasive migration.

The roles of Toll-6 and Toll-7 in JNK signaling in the context of cell proliferation and migration have been investigated.

[updated Mar. 2022 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, epithelial, Toll-receptor-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

Disease synonyms

Related Diseases

Related human health report(s)

cancer, epithelial, RAS-LLGL-related

cancer, epithelial, RAS-SCRIB-related

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\Toll-6

Gene Snapshot

Toll-6 (Toll-6) encodes a member of the Toll-like receptor family. It has neurotrophin receptor activity and contributes to dendrite guidance. Genetic interaction with 18w and Tollo suggests a Toll-6 role in convergent extension during early embryogenesis. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Low-scoring ortholog of human TLR3, TLR7, and TLR9 (multiple related genes in both species).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\Toll-7

Gene Snapshot

Toll-7 (Toll-7) encodes a plasma membrane Toll receptor that binds to viral glycoproteins, leading to the activation of antiviral defenses including autophagy. [Date last reviewed: 2018-10-18]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

TLR
TL-NFC

Comments on ortholog(s)

Low-scoring ortholog of human TLR3, TLR7, and TLR9 (multiple related genes in both species).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (16 groups)

Toll-6

protein-protein

Interacting group

Assay

References

Toll-6 - 18w

bead aggregation assay, fluorescence microscopy, inferred by author

(Paré et al., 2014)

Toll-6 - α-Spec

proximity ligation assay, fluorescence microscopy, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, Identification by mass spectrometry

(Kong et al., 2022)

Toll-6 - kek6

anti tag coimmunoprecipitation, anti tag western blot

(Ulian-Benitez et al., 2017)

Toll-6 - Myd88

anti tag coimmunoprecipitation, anti tag western blot

(Foldi et al., 2017)

Toll-6 - NT1

anti tag coimmunoprecipitation, anti tag western blot

(Foldi et al., 2017)

Toll-6 - Pi3K21B

anti tag coimmunoprecipitation, anti tag western blot

(Tamada et al., 2021)

Toll-6 - spz5

enzyme linked immunosorbent assay, anti tag coimmunoprecipitation, anti tag western blot, comigration in non denaturing gel electrophoresis

(McIlroy et al., 2013)

Toll-6 - Src42A

anti tag coimmunoprecipitation, anti tag western blot

(Tamada et al., 2021)

Toll-6 - Src64B

anti tag coimmunoprecipitation, anti tag western blot

(Tamada et al., 2021)

Toll-6 - wek

anti tag coimmunoprecipitation, anti tag western blot

(Foldi et al., 2017)

Toll-7

protein-protein

Interacting group

Assay

References

Toll-7 - fra

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Zang and Bashaw, 2023)

Toll-7 - kek6

anti tag coimmunoprecipitation, anti tag western blot

(Ulian-Benitez et al., 2017)

Toll-7 - Myd88

anti tag coimmunoprecipitation, anti tag western blot

(Foldi et al., 2017)

Toll-7 - NT1

anti tag coimmunoprecipitation, anti tag western blot, enzyme linked immunosorbent assay

(Chowdhury et al., 2019, McIlroy et al., 2013)

Toll-7 - spz

anti tag coimmunoprecipitation, anti tag western blot

(Chowdhury et al., 2019)

Toll-7 - spz5

comigration in non denaturing gel electrophoresis, anti tag western blot, anti tag coimmunoprecipitation

(Chowdhury et al., 2019, Foldi et al., 2017, McIlroy et al., 2013)

Alleles Reported to Model Human Disease (Disease Ontology) (6 alleles)

Toll-6

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

Toll-6^GD35

exacerbates carcinoma

modeled by scrib¹

(Kong et al., 2022)

Toll-6^GD14438

exacerbates carcinoma

modeled by scrib¹

(Kong et al., 2022)

ameliorates carcinoma

modeled by Ras85D^V12.UAS, l(2)gl⁴

(Mishra-Gorur et al., 2019)

modeled by Ras85D^V12.UAS, scrib¹

(Mishra-Gorur et al., 2019)

Toll-6^ACT.UAS.Flag

ameliorates carcinoma

modeled by hpo^KK101704

(Kong et al., 2022)

Toll-7

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

Toll-7^HM05230

ameliorates neurodegenerative disease

modeled by Zzzz\CTG^{rCUG.99.UAS.Tag:MYC,Tag:FLAG}, Zzzz\CAG^{99.UAS.Tag:MYC,Tag:FLAG}

(Samaraweera et al., 2013)

ameliorates carcinoma

modeled by Ras85D^V12.UAS, l(2)gl⁴

(Ding et al., 2022)

modeled by scrib^GD11666

(Ding et al., 2022)

modeled by egr^{UAS.Tag:HA,Tag:MYC}

(Ding et al., 2022)

Toll-7^GD14417

ameliorates carcinoma

modeled by Ras85D^V12.UAS, l(2)gl⁴

(Ding et al., 2022)

modeled by scrib^GD11666

(Ding et al., 2022)

modeled by egr^{UAS.Tag:HA,Tag:MYC}

(Ding et al., 2022)

Toll-7^{C993Y.UAS.Tag:FLAG}

exacerbates carcinoma

modeled by scrib^GD11666

(Ding et al., 2022)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

Toll-6^ACT.UAS.Flag

P{UAS-Toll-6.ACT.Flag}

Toll-7^{C993Y.UAS.Tag:FLAG}

P{UAS-Toll-7.CY}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸; P{GD35}v928

w¹¹¹⁸; P{GD14438}v27102

y¹ v¹; P{TRiP.HMS04251}attP2

Toll-6^HMC05842

P{TRiP.HMC05842}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC05842}attP40

Toll-7^GD16

P{GD16}

w¹¹¹⁸; P{GD16}v24473/TM3

Toll-7^GD14417

P{GD14417}

w¹¹¹⁸; P{GD14417}v39176

y¹ sc^* v¹ sev²¹; P{TRiP.HM05230}attP2

Toll-7^NIG.8595R

P{NIG.8595R}

P{NIG.8595R}1

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Toll-6^attP

amorphic allele - molecular evidence

CRISPR/Cas9

Toll-6^ex70

amorphic allele - molecular evidence

P-element activity

References (4)

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