Residual OXPHOS is required to drive primary and metastatic lung tumours in an orthotopic breast cancer model

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00586250" target="_blank" >RIV/86652036:_____/24:00586250 - isvavai.cz</a>

Result on the web

<a href="https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1362786/full" target="_blank" >https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1362786/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fonc.2024.1362786" target="_blank" >10.3389/fonc.2024.1362786</a>

Result language

angličtina

Original language name

Residual OXPHOS is required to drive primary and metastatic lung tumours in an orthotopic breast cancer model

Original language description

Background Fast adaptation of glycolytic and mitochondrial energy pathways to changes in the tumour microenvironment is a hallmark of cancer. Purely glycolytic rho 0 tumour cells do not form primary tumours unless they acquire healthy mitochondria from their micro-environment. Here we explored the effects of severely compromised respiration on the metastatic capability of 4T1 mouse breast cancer cells.Methods 4T1 cell lines with different levels of respiratory capacity were generated, the Seahorse extracellular flux analyser was used to evaluate oxygen consumption rates, fluorescent confocal microscopy to assess the number of SYBR gold-stained mitochondrial DNA nucleoids, and the presence of the ATP5B protein in the cytoplasm and fluorescent in situ nuclear hybridization was used to establish ploidy. MinION nanopore RNA sequence analysis was used to compare mitochondrial DNA transcription between cell lines. Orthotopic injection was used to determine the ability of cells to metastasize to the lungs of female Balb/c mice.Results OXPHOS-deficient ATP5B-KO3.1 cells did not generate primary tumours. Severely OXPHOS compromised rho 0D5 cells generated both primary tumours and lung metastases. Cells generated from lung metastasis of both OXPHOS-competent and OXPHOS-compromised cells formed primary tumours but no metastases when re-injected into mice. OXPHOS-compromised cells significantly increased their mtDNA content, but this did not result in increased OXPHOS capacity, which was not due to decreased mtDNA transcription. Gene set enrichment analysis suggests that certain cells derived from lung metastases downregulate their epithelial-to-mesenchymal related pathways.Conclusion In summary, OXPHOS is required for tumorigenesis in this orthotopic mouse breast cancer model but even very low levels of OXPHOS are sufficient to generate both primary tumours and lung metastases.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/GX21-04607X" target="_blank" >GX21-04607X: Horizontal transfer of mitochondria in cancer biology</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Oncology

ISSN

2234-943X

e-ISSN

2234-943X

Volume of the periodical

14

Issue of the periodical within the volume

MAY 1 2024

Country of publishing house

CH - SWITZERLAND

Number of pages

13

Pages from-to

1362786

UT code for WoS article

001222503900001

EID of the result in the Scopus database

2-s2.0-85193063148