Impairment of carbonic anhydrase IX ectodomain cleavage reinforces tumorigenic and metastatic phenotype of cancer cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F20%3A00078363" target="_blank" >RIV/00209805:_____/20:00078363 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41416-020-0804-z" target="_blank" >https://www.nature.com/articles/s41416-020-0804-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41416-020-0804-z" target="_blank" >10.1038/s41416-020-0804-z</a>
Alternative languages
Result language
angličtina
Original language name
Impairment of carbonic anhydrase IX ectodomain cleavage reinforces tumorigenic and metastatic phenotype of cancer cells
Original language description
BACKGROUND: Carbonic anhydrase IX (CA IX) is a hypoxia-induced enzyme regulating tumour pH and facilitating cell migration/ invasion. It is primarily expressed as a transmembrane cell-surface protein, but its ectodomain can be shed by ADAM17 to extracellular space. This study aims to elucidate the impact of CA IX shedding on cancer cells. METHODS: We generated a non-shed CA IX mutant by deletion of amino acids 393-402 from the stalk region and studied its phenotypic effects compared to full-length, shedding-competent CA IX using a range of assays based on immunodetection, confocal microscopy, in vitro real-time cell monitoring and in vivo tumour cell inoculation using xenografted NMRI and C57BL/6J female mice. RESULTS: We demonstrated that the impairment of shedding does not alter the ability of CA IX to bind ADAM17, internalise, form oligomers and regulate pH, but induces cancer-promoting changes in extracellular proteome. Moreover, it affects intrinsic properties of cells expressing the non-shed variant, in terms of their increased ability to migrate, generate primary tumours and form metastatic lesions in lungs. CONCLUSIONS: Our results show that the ectodomain shedding controls pro-tumorigenic and pro-metastatic roles of the cellassociated CA IX and suggest that this phenomenon should be considered when developing CA IX-targeted therapeutic strategies.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
<a href="/en/project/LO1413" target="_blank" >LO1413: RECAMO2020</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
British journal of cancer
ISSN
0007-0920
e-ISSN
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Volume of the periodical
122
Issue of the periodical within the volume
11
Country of publishing house
GB - UNITED KINGDOM
Number of pages
14
Pages from-to
1590-1603
UT code for WoS article
000521527700001
EID of the result in the Scopus database
2-s2.0-85082181399