CAIX-Mediated Control of LIN28/let-7Axis Contributes to Metabolic Adaptation of Breast Cancer Cells to Hypoxia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00534747" target="_blank" >RIV/68378050:_____/20:00534747 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1422-0067/21/12/4299" target="_blank" >https://www.mdpi.com/1422-0067/21/12/4299</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21124299" target="_blank" >10.3390/ijms21124299</a>

Result language

angličtina

Original language name

CAIX-Mediated Control of LIN28/let-7Axis Contributes to Metabolic Adaptation of Breast Cancer Cells to Hypoxia

Original language description

Solid tumors, including breast cancer, are characterized by the hypoxic microenvironment, extracellular acidosis, and chemoresistance. Hypoxia marker, carbonic anhydrase IX (CAIX), is a pH regulator providing a selective survival advantage to cancer cells through intracellular neutralization while facilitating tumor invasion by extracellular acidification. The expression of CAIX in breast cancer patients is associated with poor prognosis and metastases. Importantly, CAIX-positive hypoxic tumor regions are enriched in cancer stem cells (CSCs). Here we investigated the biological effects ofCA9-silencing in breast cancer cell lines. We found that CAIX-downregulation in hypoxia led to increased levels oflet-7(lethal-7) family members. Simultaneously with the increase oflet-7miRNAs in CAIX-suppressed cells, LIN28 protein levels decreased, along with downstream metabolic pathways: pyruvate dehydrogenase kinase 1 (PDK1) and phosphorylation of its substrate, pyruvate dehydrogenase (PDH) at Ser-232, causing attenuation of glycolysis. In addition to perturbed glycolysis, CAIX-knockouts, in correlation with decreased LIN28 (as CSC reprogramming factor), also exhibit reduction of the further CSC-associated markers NANOG (Homeobox protein NANOG) and ALDH1 (Aldehyde dehydrogenase isoform 1). Oppositely, overexpression of CAIX leads to the enhancement of LIN28, ALDH1, and NANOG. In conclusion, CAIX-driven regulation of the LIN28/let-7axis augments glycolytic metabolism and enhances stem cell markers expression during CAIX-mediated adaptation to hypoxia and acidosis in carcinogenesis.

Czech name

—

Czech description

—

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

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

21

Issue of the periodical within the volume

12

Country of publishing house

CH - SWITZERLAND

Number of pages

19

Pages from-to

4299

UT code for WoS article

000553878800001

EID of the result in the Scopus database

—