Human Disease Model Report: cancer, intestinal stem cell, EGFR-related

General Information

Name

cancer, intestinal stem cell, EGFR-related

FlyBase ID

FBhh0001370

Disease Ontology Term

intestinal cancer

Parent Disease

OMIM

Overview

Human epidermal growth factor receptor (EGFR) has been implicated in multiple cancers of epithelial derivation. EGFR is a transmembrane receptor kinase that spans the cell membrane and is activated by a number of external ligands, including EGF and transforming growth factor α. Activation of EGFR initiates several signal transduction cascades, leading to DNA synthesis and cell proliferation. There is one orthologous gene in flies, Dmel\Egfr, for which classical amorphic and hypomorphic alleles, constitutively active alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Egfr is orthologous to three additional human genes, ERBB4, ERBB3 and ERBB2; ERBB2 has also been implicated in multiple cancers.

The human Hsap\EGFR gene has been introduced into flies, but has not been used in the context of this disease model.

Using adult flies and two forms of activated Egfr (btl::Egfr^λ.UAS or Egfr^U.A887T.UAS), it has been demonstrated that overexpression of activated Egfr in intestinal stem cells and enterocytes results in stem cell hyperproliferation. The phenotype is comparable to that observed using the disease model 'cancer, intestinal stem cell, RAS-related' (FBhh0001032). The EGFR overexpression system has allowed characterization of interacting genes and related downstream signaling pathways.

Using a GAL4 line expressed in adult ISC, effects of DHA treatment on Egfr-dependent proliferation has been characterized.

[updated Jan. 2022 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, intestinal stem cell, EGFR-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase of the ErbB family. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Binding of EGFR can activate at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. [from Gene Cards, EGFR; 2021.06.29]

(FlyBase Curators, 2013-)

External links

COSMIC gene: EGFR
Gene2Function (human gene): EGFR
Gene Cards: EGFR
MedlinePlus (gene): EGFR
KEGG Disease Pathways: Pathways in Cancer
MARRVEL (human gene): EGFR
NCBI (Entrez) gene: EGFR; epidermal growth factor receptor

Disease synonyms

Related Diseases

Related human health report(s)

cancer, epithelial, EGFR-related

cancer, intestinal stem cell, RAS-related

cancer, intestinal stem cell models

Ortholog Information

Human gene(s) in FlyBase

Hsap\EGFR

Human gene (HGNC)

Symbol / Name

EGFR; epidermal growth factor receptor

D. melanogaster ortholog (based on DIOPT)

Dmel\Egfr

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 4 human genes to 1 Drosophila gene.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Egfr

Gene Snapshot

Epidermal growth factor receptor (Egfr) encodes the transmembrane tyrosine kinase receptor for signaling ligands (encoded by grk, spi, vn, and Krn) in the TGFα family, which utilises the intracellular MAP kinase pathway. The product of Egfr contributes to growth regulation, cell survival and developmental patterning. [Date last reviewed: 2019-06-06]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

EGFR-C
RTK

Comments on ortholog(s)

Orthologous to human genes EGFR, ERBB4, ERBB3, and ERBB2 (1 Drosophila to 4 human). Dmel\Egfr shares 33-37% identity and 46-51% similarity with the human genes.

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 (36 groups)

Egfr

RNA-protein

Interacting group

Assay

References

Egfr - Fmr1

anti bait coimmunoprecipitation, quantitative reverse transcription pcr, clip-seq

(Buddika et al., 2021)

Egfr - pum

rna three hybrid

(Kim et al., 2012)

protein-protein

Interacting group

Assay

References

Egfr

solid phase assay, tag visualisation by fluorescence, anti tag coimmunoprecipitation, anti tag western blot

(Alvarado et al., 2010, Alvarado et al., 2004)

Egfr - Abi

anti bait coimmunoprecipitation, western blot

(Stephan et al., 2008)

Egfr - Abl

two hybrid

(Bianco et al., 2007)

Egfr - arm

anti bait coimmunoprecipitation, western blot

(Dumstrei et al., 2002)

Egfr - ATPsynβ

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Egfr - aux

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation

(Zhao et al., 2022)

Egfr - Btk

two hybrid

(Bianco et al., 2007)

Egfr - Cbl

pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot

(Kim et al., 2017, Hime et al., 1997, Meisner et al., 1997)

Egfr - CG10916

anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting

(Friedman et al., 2011, Friedman et al., 2011)

Egfr - Crk

two hybrid

(Bianco et al., 2007)

Egfr - dock

two hybrid

(Bianco et al., 2007)

Egfr - drk

pull down, western blot, anti bait coimmunoprecipitation, two hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011, Wang and Pai, 2011, Bianco et al., 2007, MacDougall et al., 2004, Lai et al., 1995, Schweitzer et al., 1995)

Egfr - Egfrap

two hybrid

(Soler Beatty et al., 2021, Bianco et al., 2007)

Egfr - Fas2

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag western blot

(Velasquez et al., 2022)

Egfr - Graf

pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot

(Kim et al., 2017)

Egfr - Hsp83

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Egfr - kek1

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

(Ozkan et al., 2013, Alvarado et al., 2004, Alvarado et al., 2004, Derheimer et al., 2004, Ghiglione et al., 2003)

Egfr - Lnk

two hybrid

(Bianco et al., 2007)

Egfr - Mbs

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Egfr - Mcad

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Egfr - Pi3K21B

two hybrid

(Bianco et al., 2007)

Egfr - porin

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Egfr - Ptp10D

anti tag coimmunoprecipitation, anti tag western blot

(Jeon and Zinn, 2009)

Egfr - Pyk

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Egfr - RFeSP

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Egfr - Sec10

pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot

(Mao et al., 2019)

Egfr - Sec15

pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot

(Mao et al., 2019)

Egfr - Shc

anti bait coimmunoprecipitation, western blot, two hybrid, anti tag coimmunoprecipitation, anti tag western blot, pull down

(Bianco et al., 2007, van der Geer et al., 1996, Lai et al., 1995)

Egfr - shg

anti bait coimmunoprecipitation, western blot

(Dumstrei et al., 2002)

Egfr - spi

surface plasmon resonance, predetermined participant, x-ray crystallography, cosedimentation in solution, solid phase assay, tag visualisation by fluorescence

(Alvarado et al., 2010, Miura et al., 2006, Klein et al., 2004)

Egfr - sqd

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Egfr - Src42A

two hybrid

(Bianco et al., 2007)

Egfr - vap

anti tag coimmunoprecipitation, anti tag western blot, two hybrid

(Rowshanravan et al., 2014, Bianco et al., 2007)

Egfr - Vav

two hybrid, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting

(Fernández-Espartero et al., 2013, Friedman et al., 2011, Bianco et al., 2007, Sarkar et al., 2007)

Alleles Reported to Model Human Disease (Disease Ontology) (19 alleles)

Hsap\EGFR

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Hsap\EGFR^Δ.UAS

model of brain glioma

CEA with Pi3K92E^{UAS.Tag:MYC,Tag:PM(hKRAS)}

(Read et al., 2013)

CEA

(Read et al., 2013)

model of high grade glioma

CEA with Pi3K92E^{UAS.Tag:MYC,Tag:PM(hKRAS)}

(Formica et al., 2021, Terrasi et al., 2019)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Hsap\EGFR^Δ.UAS

model of brain glioma

is ameliorated by RIOK1^GD8541

(Read et al., 2013)

is ameliorated by RIOK2^KK101850

(Read et al., 2013)

is ameliorated by RIOK1^KK100810

(Read et al., 2013)

is ameliorated by RIOK2^GD7407

(Read et al., 2013)

Egfr

Models Based on Experimental Evidence ( 6 )

Allele

Disease

Evidence

References

Egfr^2.A887T.UAS

model of intestinal cancer

CEA

(Nászai et al., 2021)

model of cancer

CEA with scrib⁶⁷³

(Sheng and Du, 2020)

CEA

(Brás et al., 2021)

Egfr^UAS.cBa

model of alcohol use disorder

CEA

(Corl et al., 2009)

model of intestinal cancer

CEA

(Nászai et al., 2021)

model of carcinoma

CEA with mir-ban^C.UAS.EGFP

(Herranz et al., 2012)

CEA with Socs36E^GD8929

(Xu et al., 2022, Groth et al., 2020, Herranz et al., 2012)

CEA with Socs36E^EY11

(Herranz et al., 2012)

CEA with psq^KK111691

(Boukhatmi et al., 2020, Fereres et al., 2019)

CEA

(Groth et al., 2020)

DOES NOT model carcinoma

CEA with Diap1^UAS.cUa

(Herranz et al., 2012)

model of cancer

CEA with psq^KK111691

(Herranz et al., 2014)

CEA with mir-8^UAS.cUa

(Eichenlaub et al., 2016)

CEA with mir-ban^UAS.cUa

(Eichenlaub et al., 2016)

CEA with Aldh7A1^KK109006

(Andrejeva et al., 2018)

Egfr^U.A887T.UAS

model of cardiomyopathy

CEA

(Yu et al., 2013)

Egfr^GD1654

model of alcohol use disorder

CEA

(Corl et al., 2009)

Egfr^KK100051

model of renal fibrosis

CEA with DopEcR^KK111211

(Zheng et al., 2020)

Egfr^Act.cUa.UAS

model of high grade glioma

CEA with Pi3K92E^CAAX.UAS

(Pryszlak et al., 2021)

Modifiers Based on Experimental Evidence ( 16 )

Allele

Disease

Interaction

References

Egfr^{FRT.RNAi.slbo}

ameliorates Parkinson's disease 1

modeled by Hsap\SNCA^UAS.cJa

(Rousseaux et al., 2018)

Egfr^1.UAS

exacerbates cancer

modeled by Myc^UAS.cZa, p53^{RNAi.UAS.RasG12D}

(Diaz et al., 2024)

Egfr^2.A887T.UAS

model of intestinal cancer

is ameliorated by Rala^KK108989

(Nászai et al., 2021)

is exacerbated by Rala^UAS.cRa

(Nászai et al., 2021)

Egfr^2.UAS

exacerbates cancer

modeled by Ras85D^{G12V.UAS.Tag:FLAG,Tag:polyHis}

(Washington et al., 2020)

modeled by Ras85D^{Y4F.G12V.UAS.Tag:FLAG,Tag:polyHis}

(Washington et al., 2020)

Egfr^DN.UAS

ameliorates carcinoma

modeled by scrib¹

(Brumby and Richardson, 2003)

ameliorates gastrointestinal system cancer

modeled by Apc2^g10, Apc^Q8

(Wang et al., 2013)

ameliorates colorectal cancer

modeled by Src64B^UAS.cCa

(Cordero et al., 2014)

Egfr^UAS.cBa

ameliorates spinocerebellar ataxia type 13

modeled by Hsap\KCNC3^R423H.UAS

(Khare et al., 2017)

model of intestinal cancer

is ameliorated by Rala^KK108989

(Nászai et al., 2021)

is exacerbated by Rala^UAS.cRa

(Nászai et al., 2021)

is ameliorated by Ras85D^KK108029

(Nászai et al., 2021)

Egfr^f2

exacerbates germ cell cancer

modeled by sfl^HMS00543

(Levings and Nakato, 2018)

Egfr^f24

ameliorates Billuart-type X-linked syndromic intellectual developmental disorder

modeled by Graf¹

(Kim et al., 2021)

Egfr^t1

ameliorates colorectal cancer

modeled by Src42A^CA.UAS

(Cordero et al., 2014)

Egfr^JF01368

ameliorates glioblastoma

modeled by Pi3K92E^CAAX.UAS, btl::Egfr^λ.UAS

(Chi et al., 2019)

ameliorates colorectal cancer

modeled by SH3PX1^HMJ21552

(Zhang et al., 2019)

Egfr^UAS.cUa

exacerbates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.UAS.cUa}

(Cheng et al., 2021)

Egfr^GD1654

ameliorates prostate cancer

modeled by Ras85D^V12.UAS

(Rambur et al., 2020)

Egfr^KK100051

exacerbates alcohol use disorder

modeled by DopEcR^c02142

(Petruccelli et al., 2016)

ameliorates colorectal cancer

modeled by Src42A^CA.UAS

(Cordero et al., 2014)

Egfr^DN.cUa.UAS

DOES NOT ameliorate cancer

modeled by Hipk^UAS.Tag:HA

(Blaquiere et al., 2018)

Egfr^JF02283

ameliorates lung adenocarcinoma

modeled by Hsap\KIF5B::Hsap\RET^UAS.cDa

(Das and Cagan, 2017)

Egfr^RNAi.UAS.cUa

ameliorates intestinal cancer

modeled by Src64B^UAS.cUa

(Kohlmaier et al., 2015)

modeled by Src42A^CA.UAS

(Kohlmaier et al., 2015)

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

Hsap\EGFR^Δ.UAS

P{UAS-hEGFR.Delta}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

y¹ w^*; P{UAS-Egfr.B}32-26-1

Egfr^2.UAS

P{Egfr.2.UAS}

w^*; P{Egfr.2.UAS}7-10

Egfr^2.A887T.UAS

P{Egfr.2.A887T.UAS}

w^*; P{Egfr.2.A887T.UAS}8-2

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Egfr^{RNAi.13xlexAop.cZa}

P{13xlexAop-Egfr.RNAi.Z}

w¹¹¹⁸; P{GD1654}v43267

Egfr^JF01368

P{TRiP.JF01368}

y¹ v¹; P{TRiP.JF01368}attP2

y¹ v¹; P{TRiP.JF01083}attP2

Egfr^JF01084

P{TRiP.JF01084}

y¹ v¹; P{TRiP.JF01084}attP2

Egfr^JF01696

P{TRiP.JF01696}

y¹ v¹; P{TRiP.JF01696}attP2

y¹ v¹; P{TRiP.JF02283}attP2

Egfr^JF02384

P{TRiP.JF02384}

y¹ v¹; P{TRiP.JF02384}attP2

Egfr^{FRT.RNAi.slbo}

M{slbo(FRT.lacZ)Egfr.RNAi}

w¹¹¹⁸; M{slbo(FRT.lacZ)Egfr.RNAi}ZH-51D

Egfr^RNAi.slbo

M{slbo(-FRT)Egfr.RNAi}

Egfr^HMS05003

P{TRiP.HMS05003}

y¹ v¹; P{TRiP.HMS05003}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Egfr^top-EB

loss of function allele

ethyl methanesulfonate

Egfr^f24

loss of function allele

ethyl methanesulfonate

w^*; smo^D16 P{neoFRT}42D mam¹⁰ Egfr^f24/CyO, P{ActGFP}JMR1

Egfr^f36

amorphic allele - genetic evidence

gamma ray

Egfr^top-101

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^top-EE42

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^top-EC20

loss of function allele

ethyl methanesulfonate

Egfr^f3

loss of function allele

ethyl methanesulfonate

cn¹ Egfr^f3 bw¹ speck¹/CyO

Egfr^f6

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^f9

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^f11

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^top-EA

loss of function allele

ethyl methanesulfonate

Egfr^top-CA

loss of function allele

ethyl methanesulfonate

Egfr^top-38

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^f8

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^JE1

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^f38

amorphic allele - genetic evidence

gamma ray

Egfr^JE13

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^f12

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^f10

amorphic allele - genetic evidence

ethyl methanesulfonate

Egfr^f5

amorphic allele - genetic evidence

ethyl methanesulfonate

cn¹ Egfr^f5 bw¹ speck¹/CyO

Egfr^top-18A

amorphic allele - genetic evidence

Egfr^f37

amorphic allele - genetic evidence

gamma ray

Egfr^t1

ethyl methanesulfonate

Egfr^t1 bw¹/CyO

Egfr^f2

amorphic allele - genetic evidence

ethyl methanesulfonate

cn¹ Egfr^f2 bw¹ speck¹/CyO

References (6)

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