Tumor-derived MMPs regulate cachexia in a Drosophila cancer model

Zavortink, Michael; Golenkina, Sofia; Froldi, Francesca; Dark, Callum; Cheung, Shane; Parker, Benjamin L.; Blazev, Ronnie; Bakopoulos, Daniel; Christie, Elizabeth L.; Wimmer, Verena C.; Duckworth, Brigette C.; Richardson, Helena E.; Cheng, Louise

doi:10.1016/j.devcel.2021.08.008

Cited by 33 publications

(81 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A third larval cancer cachexia model, Ras V12 dlg RNAi ( Lodge et al, 2021 ), was also generated in the eye-antennal epithelial discs by expressing activated Ras in a previously described genetic background in which the activity of the cell polarity tumor suppressor gene disc-large 1 ( dlg ; also known as dlg1 ) ( Woods and Bryant, 1991 ) is reduced ( Fig. 1 ).…”

Section: Drosophila Models Of Organ Wasting Induced By Tumorsmentioning

confidence: 99%

“…Mmp1 downregulates fat body transforming growth factor beta (TGF-β) signaling, independently of ImpL2, by controlling the availability of one of its ligands, Glass bottom boat (Gbb). In addition, elevated Mmp1 levels perturb fat body and muscle basement membrane (BM) and localization of extracellular matrix (ECM) proteins, leading to degeneration of the fat body and muscle ( Lodge et al, 2021 ). Increased Mmp1 expression has also been observed in Ras V12 scrib −/− and Ras V12 Csk −/− larval tumor models, as well as in the adult yki act tumor model ( Uhlirova and Bohmann, 2006 ; Hirabayashi et al, 2013 ; Song et al, 2019 ).…”

Section: Drosophila Models Of Organ Wasting Induced By Tumorsmentioning

confidence: 99%

“…Each of the models described above has advantages and limitations. The presence of tumors in larvae is usually associated with delays in larval growth, which may confound interpretation of the tumors' effects on peripheral tissues ( Hodgson et al, 2021 ; Khezri et al, 2021 ; Newton et al, 2020 ; Lodge et al, 2021 ). In addition, the time scale for larval models is much shorter than that for adult ones and may not be sufficient to fully evaluate the effect of tumors on the host.…”

Section: Drosophila Models Of Organ Wasting Induced By Tumorsmentioning

confidence: 99%

“…On the other hand, as transplantable tumor cells can be injected in animals of various genotypes, this approach can simplify the development of complex animal models in which to dissect tumor–host communication ( Kim et al, 2021 ). Achieving similar goals in non-transplanted models requires two binary systems ( Box 1 ) ( del Valle Rodríguez et al, 2012 ), such as GAL4/UAS and LexA/LexAop ( Lee et al, 2021 ) or GAL4/UAS and QF/QUAS ( Hodgson et al, 2021 ; Lodge et al, 2021 ). Despite their limitations, research in fly models has identified a number of cachectic factors ( Fig.…”

Section: Drosophila Models Of Organ Wasting Induced By Tumorsmentioning

confidence: 99%

See 3 more Smart Citations

Cancer cachexia: lessons from Drosophila

Liu

Saavedra

Perrimon

2022

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Cachexia, a wasting syndrome that is often associated with cancer, is one of the primary causes of death in cancer patients. Cancer cachexia occurs largely due to systemic metabolic alterations stimulated by tumors. Despite the prevalence of cachexia, our understanding of how tumors interact with host tissues and how they affect metabolism is limited. Among the challenges of studying tumor–host tissue crosstalk are the complexity of cancer itself and our insufficient knowledge of the factors that tumors release into the blood. Drosophila is emerging as a powerful model in which to identify tumor-derived factors that influence systemic metabolism and tissue wasting. Strikingly, studies that are characterizing factors derived from different fly tumor cachexia models are identifying both common and distinct cachectic molecules, suggesting that cachexia is more than one disease and that fly models can help identify these differences. Here, we review what has been learned from studies of tumor-induced organ wasting in Drosophila and discuss the open questions.

show abstract

Section: Drosophila Models Of Organ Wasting Induced By Tumorsmentioning

confidence: 99%

Section: Drosophila Models Of Organ Wasting Induced By Tumorsmentioning

confidence: 99%

Section: Drosophila Models Of Organ Wasting Induced By Tumorsmentioning

confidence: 99%

Section: Drosophila Models Of Organ Wasting Induced By Tumorsmentioning

confidence: 99%

See 2 more Smart Citations

Cancer cachexia: lessons from Drosophila

Liu

Saavedra

Perrimon

2022

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…Recently, another wasting model in Drosophila , relates the FB remodelling and muscle detachment to the tumor-secreted matrix metalloproteinase 1 (Mmp1). Mmp1 can modulate TGFβ signalling in the FB and disrupts the basement membrane/extracellular matrix in FB and muscle ( Lodge et al, 2021 ). All theses studies show that the conservation of the signalling pathways and the existing genetic tools, make of Drosophila an important model to study the process of organ wasting and to identify new molecular mechanisms involved in this process.…”

Section: Role Of Adult Fat Bodymentioning

confidence: 99%

Origin and Development of the Adipose Tissue, a Key Organ in Physiology and Disease

Parra-Peralbo¹,

Talamillo²,

Barrio³

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Adipose tissue is a dynamic organ, well known for its function in energy storage and mobilization according to nutrient availability and body needs, in charge of keeping the energetic balance of the organism. During the last decades, adipose tissue has emerged as the largest endocrine organ in the human body, being able to secrete hormones as well as inflammatory molecules and having an important impact in multiple processes such as adipogenesis, metabolism and chronic inflammation. However, the cellular progenitors, development, homeostasis and metabolism of the different types of adipose tissue are not fully known. During the last decade, Drosophila melanogaster has demonstrated to be an excellent model to tackle some of the open questions in the field of metabolism and development of endocrine/metabolic organs. Discoveries ranged from new hormones regulating obesity to subcellular mechanisms that regulate lipogenesis and lipolysis. Here, we review the available evidences on the development, types and functions of adipose tissue in Drosophila and identify some gaps for future research. This may help to understand the cellular and molecular mechanism underlying the pathophysiology of this fascinating key tissue, contributing to establish this organ as a therapeutic target.

show abstract