FB2025_01 , released February 20, 2025
Human Disease Model Report: cachexia, yki-induced ISC tumor model
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General Information
Name
cachexia, yki-induced ISC tumor model
FlyBase ID
FBhh0001115
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes a tumor model using an activated form of Dmel\yki expressed in adult intestinal stem cells (ISC) and the use of this model to investigate the phenomenon of cachexia. Dmel\yki is orthologous to human YAP1 and is a core component of the Hippo Signaling Pathway (FBgg0000913); see the human disease model report 'cancer, multiple, Hippo signaling pathway' (FBhh0000764).

When an activated form of Dmel\yki is specifically expressed in adult intestinal stem cells of the midgut, sequential steps of tumor development are observed, each lasting approximately 2 days: proliferation state; tumorigenesis state, during which tumors expand to the whole midgut; ascites state, during which the abdomen expands and muscle dysfunction is observed; wasting or bloating state, with further abdomen expansion, severe TAG decrease, carbohydrate increase, and muscle dysfunction.

MEK/ERK (MAPK/ERK) signaling is observed to increase during this progression, in both tumors and non-tumorous host tissues. Tumor MEK/ERK activation is required for tumor growth. Non-autonomous activation of MEK/ERK in host tissues results in muscle wasting and lipid loss. This system has allowed characterization and comparison of molecular mechanisms involved in ISC tumor development and resulting changes in non-tumorous tissues. In an assessment of the contribution of various candidate ligand genes, it was determined that Pvf1 and its receptor Pvr play a key role in this process. One of the conclusions of these studies is that Pvf1 and ImpL2 are independent regulators of the non-autonomous tissue wasting observed with yki-induced ISC tumors; see the human disease model report 'cachexia, IGFBP-related' (FBhh0000535).

Several MEK pharmaceutical inhibitors were shown to ameliorate the wasting phenotypes.

The Warburg effect (preferential use of aerobic glycolysis by cancer cells) may be one of the contributing factors in the development of cachexia. See human disease model reports 'cancer, aerobic glycolysis (Warburg effect), larval growth ' (FBhh0000502) and 'cancer, epithelial, glycolytic tumor model' (FBhh0000959).

[updated Apr. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cachexia, yki-induced ISC tumor model
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Cachexia is characterized by a dramatic loss of skeletal muscle mass and adipose tissue, resulting in substantial weight loss. It is also known as "wasting syndrome", causing disproportionate muscle wasting, weakness, fatigue, and loss of appetite in affected individuals. Cachexia occurs in many cancers, usually at the advanced stages of disease. [ http://www.news-medical.net/health/Cachexia-Wasting-Syndrome-.aspx ] [ https://www.cancer.gov/about-cancer/treatment/research/cachexia ]

Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
cachexia, MAPK/ERK signaling model
cachexia, MEK/ERK signaling model
wasting syndrome
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      yorkie (yki) encodes a transcriptional co-activator protein that is negatively regulated by Hippo signaling, which promotes its cytoplasmic localization. It functions together with DNA binding proteins, such as the product of sd, to activate transcription of a wide range of downstream targets, including genes that promote growth. [Date last reviewed: 2019-03-21]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate-scoring ortholog of human YAP1; lower-scoring ortholog of WWTR1 (1 Drosophila to 2 human). Dmel\yki shares 31% identity and 45% similarity with YAP1; it shares 25% identity and 34% similarity with WWTR1.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (79 groups)
        RNA-RNA
        Interacting group
        Assay
        References
        luminiscence technology
        fluorescence technology
        RNA-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting, protein complementation assay
        anti tag coimmunoprecipitation, anti tag western blot, western blot, peptide massfingerprinting
        anti tag coimmunoprecipitation, western blot, peptide massfingerprinting, anti tag western blot, pull down
        enzymatic study, western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti bait coimmunoprecipitation, peptide massfingerprinting
        pull down, Identification by mass spectrometry, anti tag coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, peptide massfingerprinting, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, Identification by mass spectrometry, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot, western blot
        enzymatic study, western blot
        anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, tag visualisation
        coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
        anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, Identification by mass spectrometry, pull down, peptide massfingerprinting
        anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, pull down
        pull down, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        enzymatic study, autoradiography, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
        proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot, pull down, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, peptide massfingerprinting
        anti bait coimmunoprecipitation, peptide massfingerprinting
        anti bait coimmunoprecipitation, peptide massfingerprinting
        anti bait coimmunoprecipitation, peptide massfingerprinting
        anti bait coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, peptide massfingerprinting, tandem affinity purification, Identification by mass spectrometry, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot, pull down, anti bait coimmunoprecipitation, peptide massfingerprinting, western blot
        pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based, anti tag western blot
        anti bait coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        enzymatic study, autoradiography
        anti tag coimmunoprecipitation, western blot, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation
        anti tag coimmunoprecipitation, peptide massfingerprinting
        experimental knowledge based
        anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot, pull down, autoradiography, two hybrid, surface plasmon resonance, predetermined participant, anti bait coimmunoprecipitation, fluorescent resonance energy transfer, western blot
        anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, peptide massfingerprinting
        molecular sieving, molecular weight, isothermal titration calorimetry, predetermined participant, anti tag coimmunoprecipitation, anti tag western blot, pull down, Identification by mass spectrometry, peptide massfingerprinting, two hybrid, nuclear magnetic resonance
        anti bait coimmunoprecipitation, peptide massfingerprinting, pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot
        pull down, western blot
        proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, western blot, bimolecular fluorescence complementation
        pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, peptide massfingerprinting, anti tag coimmunoprecipitation, anti tag western blot
        enzymatic study, autoradiography, pull down, peptide massfingerprinting, anti tag coimmunoprecipitation, anti tag western blot, western blot, two hybrid
        Alleles Reported to Model Human Disease (Disease Ontology) (23 alleles)
        Models Based on Experimental Evidence ( 14 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 19 )
        Allele
        Disease
        Interaction
        References
        model of  cancer
        is ameliorated by lzUAS.cBa
        is exacerbated by trioUAS.cUa
        model of  cancer
        is ameliorated by AlaRSGD8009
        is exacerbated by ArgRSGD14098
        is ameliorated by AsnRSGD7064
        is ameliorated by AsnRSKK100240
        is ameliorated by AspRSGD1339
        is exacerbated by CysRSGD13923
        is exacerbated by GlnRSKK109443
        is ameliorated by GlyRSKK107421
        is exacerbated by HisRSKK102374
        is exacerbated by LysRSKK101852
        is exacerbated by ThrRSGD1342
        is exacerbated by TyrRSGD11353
        is ameliorated by ImpL2GD6004
        is ameliorated by Ilp8KK112161
        is ameliorated by Ilp8MI00727
        is ameliorated by Lgr3Δ50
        model of  cancer
        is ameliorated by AktHMS00007
        is ameliorated by foxoTM.UAS
        is ameliorated by panΔN.UAS
        is ameliorated by wgHMS00794
        is ameliorated by wgJF01257
        is ameliorated by ITPGD3825
        is ameliorated by ITPJF01817
        is ameliorated by ImpL2HMC05809
        is ameliorated by domeGD2612
        is ameliorated by hopHMS00761
        is ameliorated by upd3HMS00646
        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
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        loss of function allele
        References (29)