Heterogeneous protein dynamics links to mitochondrial activity, glucose transporter, and ALDH cancer stem cell properties

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F25%3A00080350" target="_blank" >RIV/00209805:_____/25:00080350 - isvavai.cz</a>

Result on the web

<a href="https://bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14460-x" target="_blank" >https://bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14460-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12885-025-14460-x" target="_blank" >10.1186/s12885-025-14460-x</a>

Result language

angličtina

Original language name

Heterogeneous protein dynamics links to mitochondrial activity, glucose transporter, and ALDH cancer stem cell properties

Original language description

BACKGROUND: Cancer stem-like cells (CSCs) represent a subset of tumor cells that have the ability to self-renew, a long lifespan and a relatively quiescent phenotype, and show resistance to conventional therapies. Various markers are used to identify CSCs, and have shown that different CSC subtypes may be present within a tumor. One functional property of CSCs is their relative lack of proteasomal activity compared to the tumor bulk. METHODS: We introduced an unstable fluorescent molecule into FaDu oropharyngeal squamous cell carcinoma cells and analyzed the association of proteasome activity with aldehydehyde dehydrogenase (ALDH) activity as another common CSC marker, and with other stem-cell related properties of glucose metabolism. We also analyzed publicly available gene expression profiling data of ALDH(+) CSCs for alterations in mRNAs associated with proteostasis. RESULTS: We show that FaDu CSCs identified by low proteasome activity are associated with the population identified by high ALDH activity. Futher characterization shows that these CSCs have a relatively high mitochondrial membrane potential and low levels of glucose transporter, indicating a non-Warburg metabolic phenotype. We also show that proteasome-low FaDu CSCs exhibit decreased rates of protein synthesis. Gene expression profiling of other cancer cell lines reveal common statistically significant differences in proteostasis in ALDH(+) CSCs compared to the bulk of the tumor cells, including reduced levels of Hsp70 and/or Hsp90 in CSCs defined by ALDH, together with reduced levels of UCHL5 mRNA. CONCLUSIONS: These data provide additional insights into the functional characteristics of proteasome-low/ALDH-high CSCs, indicating a metabolic phenotype of reduced reliance on aerobic glycolysis and a decreased protein synthesis rate. We also identify specific chaperone and ubiquitin ligase activities that can be used to identify CSCs, with corresponding implications for therapeutic strategies that target CSCs through their altered metabolic properties.

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

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

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

Name of the periodical

BMC cancer

ISSN

—

e-ISSN

1471-2407

Volume of the periodical

25

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

1085

UT code for WoS article

001522915300033

EID of the result in the Scopus database

2-s2.0-105009728312