High Fructose Drives the Serine Synthesis Pathway in Acute Myeloid Leukemic Cells

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2020 Dec 28

PMID 33357456

Citations 29

Authors

Sangmoo Jeong

Angela Maria Savino

Rachel Chirayil

Ersilia Barin

Yuanming Cheng

Sun-Mi Park

Alexandra Schurer

Edouard Mullarky

Lewis C Cantley

Michael G Kharas

Kayvan R Keshari

Affiliations

Soon will be listed here.

Abstract

A significant increase in dietary fructose consumption has been implicated as a potential driver of cancer. Metabolic adaptation of cancer cells to utilize fructose confers advantages for their malignant growth, but compelling therapeutic targets have not been identified. Here, we show that fructose metabolism of leukemic cells can be inhibited by targeting the de novo serine synthesis pathway (SSP). Leukemic cells, unlike their normal counterparts, become significantly dependent on the SSP in fructose-rich conditions as compared to glucose-rich conditions. This metabolic program is mediated by the ratio of redox cofactors, NAD/NADH, and the increased SSP flux is beneficial for generating alpha-ketoglutarate from glutamine, which allows leukemic cells to proliferate even in the absence of glucose. Inhibition of PHGDH, a rate-limiting enzyme in the SSP, dramatically reduces leukemia engraftment in mice in the presence of high fructose, confirming the essential role of the SSP in the metabolic plasticity of leukemic cells.

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