Human Disease Model Report: cancer, epithelial, glycolytic tumor model

General Information

Name

cancer, epithelial, glycolytic tumor model

FlyBase ID

FBhh0000959

Disease Ontology Term

carcinoma

Parent Disease

OMIM

Overview

This Drosophila model is designed to recapitulate the switch to high levels of aerobic glycolysis observed in many aggressive cancers (the Warburg effect). An activated form of Dmel\Pvr, a single-pass transmembrane receptor tyrosine kinase that feeds into multiple oncogenic signaling pathways, is used to induce a high glycolytic state in a subset of cells in the wing disc; localized tumorous overgrowth is observed in the affected wing discs. Aerobic glycolysis in tumors is characterized by the conversion of pyruvate to lactate by the enzyme lactate dehydrogenase (LDH); elevated levels of LDH are observed in the the tumors produced by cells expressing activated Pvr (Pvr^{λ.UASp.Tag:MYC}). Other markers of the glycolytic pathway vs. those of oxidative phosphorylation have been assessed; members of the network of genes required to establish and maintain this metabolic reprogramming process have been identified.

See also the gene group pathway report for the Pvr signaling pathway (FBgg0000972) and the human disease model report 'cancer, aerobic glycolysis (Warburg effect), ERR model' (FBhh0000502). The Warburg effect may be one of the contributing factors in the development of cachexia. See human disease model reports 'cachexia, IGFBP-related' (FBhh0000535) and 'cachexia, yki-induced ISC tumor model' (FBhh0001115).

[updated Feb. 2020 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, epithelial, glycolytic tumor model

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

PDGF/VEGF-receptor related (Pvr) encodes a receptor tyrosine kinase activated by the binding of PDGF- and VEGF-related factors (Pvf1, Pvf2 or Pvf3). Pvr has been shown to activate the canonical Ras/Raf/MAP kinase (ERK) cascade, the PI3K kinase pathway, TORC1, Rho family small GTPases, and the JNK cascade in a context-dependent manner. [from FBgg0000972]

(FlyBase Curators, 2013-)

External links

KEGG Disease Pathways: Central carbon metabolism in cancer

Disease synonyms

Search term: cancer, aerobic glycolysis

Search term: Warburg effect

Related Diseases

Related human health report(s)

cachexia, IGFBP-related

cachexia, yki-induced ISC tumor model

cancer, aerobic glycolysis (Warburg effect), larval growth model

cancer, multiple, HIPK-related

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Pvr

Gene Snapshot

PDGF- and VEGF-receptor related (Pvr) encodes a receptor tyrosine kinase activated by the binding of PDGF- and VEGF-related factors (encoded by Pvf1, Pvf2 or Pvf3). It is involved in cell migration regulation and it has been shown to activate the canonical Ras/Raf/MAP kinase (ERK) cascade, the PI3K kinase pathway, TORC1, Rho family small GTPases and the JNK cascade, in a context-dependent manner. [Date last reviewed: 2019-09-12]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

PVR-C
RTK

Comments on ortholog(s)

Moderate- to high-scoring ortholog of 6 genes in human, including FLT1, FLT4, and KDR; lower-scoring ortholog of additional human genes (1 Drosophila to many human).

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 (37 groups)

Pvr

protein-protein

Interacting group

Assay

References

Pvr - Abl

two hybrid

(Bianco et al., 2007)

Pvr - Btk

two hybrid

(Bianco et al., 2007)

Pvr - by

two hybrid

(Bianco et al., 2007)

Pvr - CanA-14F

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Pvr - Cbl

two hybrid

(Jekely et al., 2005)

Pvr - CG5447

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - CG7668

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - CG8034

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - CG10916

anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot

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

Pvr - CG14767

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - CG14879

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - Crk

anti tag coimmunoprecipitation, anti tag western blot

(Ishimaru et al., 2004)

Pvr - csw

two hybrid

(Bianco et al., 2007)

Pvr - DnaJ-1

two hybrid

(Cobreros et al., 2008)

Pvr - dock

two hybrid

(Bianco et al., 2007)

Pvr - drk

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

(Friedman et al., 2011, Bianco et al., 2007, Ishimaru et al., 2004)

Pvr - Frl

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - HDAC3

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Pvr - Pi3K21B

two hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016, Glatter et al., 2011, Bianco et al., 2007, Jekely et al., 2005, Ishimaru et al., 2004)

Pvr - Pi3K92E

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016)

Pvr - Pp2B-14D

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Pvr - Ptpmeg

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Li et al., 2015)

Pvr - Pvf1

affinity technology, inferred by author

(Duchek et al., 2001)

Pvr - PVRAP

anti bait coimmunoprecipitation, anti tag western blot

(Tran et al., 2013)

Pvr - sax

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - Shc

experimental knowledge based, anti tag coimmunoprecipitation, anti tag western blot, two hybrid

(Guruharsha et al., 2011, Bianco et al., 2007, Ishimaru et al., 2004)

Pvr - sl

anti tag coimmunoprecipitation, anti tag western blot

(Ishimaru et al., 2004)

Pvr - spri

two hybrid

(Bianco et al., 2007, Jekely et al., 2005)

Pvr - Spt6

two hybrid

(Bianco et al., 2007)

Pvr - Src42A

two hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011, Bianco et al., 2007)

Pvr - sty

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - Syb

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - Syx7

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - Tmep

experimental knowledge based

(Guruharsha et al., 2011)

Pvr - vap

anti tag coimmunoprecipitation, anti tag western blot, two hybrid

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

Pvr - Vav

anti bait coimmunoprecipitation, western blot, two hybrid

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

Pvr - vptr

experimental knowledge based

(Guruharsha et al., 2011)

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

Pvr

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Pvr^{λ.UASp.Tag:MYC}

model of cancer

CEA

(Wang et al., 2023, Lodge et al., 2021)

model of carcinoma

CEA

(Bawa et al., 2020)

model of nephrolithiasis

CEA

(Xu et al., 2024)

Modifiers Based on Experimental Evidence ( 6 )

Allele

Disease

Interaction

References

Pvr^{λ.UASp.Tag:MYC}

model of carcinoma

is ameliorated by tn^ΔA

(Bawa et al., 2020)

model of cancer

is ameliorated by N^intra.GS.UAS

(Wang et al., 2023)

is ameliorated by kuz^UAS.cFa

(Wang et al., 2023)

model of nephrolithiasis

is ameliorated by Jra^JF01184

(Xu et al., 2024)

is ameliorated by Uro^{UAS.127D01-tag}

(Xu et al., 2024)

is ameliorated by bsk^DN.UAS

(Xu et al., 2024)

Pvr^UAS.cDa

ameliorates acute myeloid leukemia

modeled by Hsap\HOXA9::Hsap\NUP98^WT.UAS

(Baril et al., 2017)

Pvr^GD75

ameliorates Huntington's disease

modeled by Hsap\HTT^{128Q.1-231.UAS}

(Onur et al., 2021)

Pvr^GD14375

exacerbates acute myeloid leukemia

modeled by Hsap\HOXA9::Hsap\NUP98^WT.UAS

(Baril et al., 2017)

Pvr^KK101575

exacerbates cancer

modeled by dlg1^A40.2

(Parisi et al., 2014)

Pvr^HMS01662

ameliorates lung adenocarcinoma

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

(Das and Cagan, 2017)

ameliorates intestinal cancer

modeled by yki^{3SA.lexAop.sfGFP}

(Xu et al., 2024)

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

w¹¹¹⁸; P{UASp-Pvr.λ}mP1

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸; P{GD75}v977

w¹¹¹⁸; P{GD2571}v13502

Pvr^GD14375

P{GD14375}

w¹¹¹⁸; P{GD14375}v43459

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01662}attP40

Pvr^NIG.8222R

P{NIG.8222R}

P{NIG.8222R}2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Pvr^c02195

loss of function allele

piggyBac activity

w¹¹¹⁸; PBac{PB}Pvr^c02195/CyO

Pvr⁴

loss of function allele

ethyl methanesulfonate

References (18)

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