J 2016

Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle

SLANINOVA, Vera, Michaela KRAFČÍKOVÁ, Raquel PEREZ-GOMEZ, Pavel STEFFAL, Lukáš TRANTÍREK et. al.

Basic information

Original name

Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle

Authors

SLANINOVA, Vera (203 Czech Republic), Michaela KRAFČÍKOVÁ (703 Slovakia, belonging to the institution), Raquel PEREZ-GOMEZ (203 Czech Republic), Pavel STEFFAL (203 Czech Republic), Lukáš TRANTÍREK (203 Czech Republic, guarantor, belonging to the institution), Sarah J. BRAY (826 United Kingdom of Great Britain and Northern Ireland) and Alena KREJCI (203 Czech Republic)

Edition

OPEN BIOLOGY, LONDON, ROYAL SOC, 2016, 2046-2441

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.481

RIV identification code

RIV/00216224:14740/16:00093886

Organization unit

Central European Institute of Technology

DOI

UT WoS

000371256100004

Keywords in English

metabolism; Notch targets; Warburg effect; glycolytic shift; tissue growth

Tags

Tags

International impact, Reviewed
Změněno: 5/2/2021 12:38, Mgr. Michaela Krafčíková, Ph.D.

Abstract

V originále

Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues.