From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments

Emma Hajaj; Sabina Pozzi; Ayelet Erez

doi:10.1101/cshperspect.a041538

From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments

Emma Hajaj, Sabina Pozzi, Ayelet Erez^*

^*Corresponding author for this work

Department of Immunology and Regenerative Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Catabolic pathways change in anabolic diseases such as cancer to maintain metabolic homeostasis. The liver urea cycle (UC) is the main catabolic pathway for disposing excess nitrogen. Outside the liver, the UC enzymes are differentially expressed based on each tissue's needs for UC intermediates. In tumors, there are changes in the expression of UC enzymes selected for promoting tumorigenesis by increasing the availability of essential UC substrates and products. Consequently, there are compensatory changes in the expression of UC enzymes in the cells that compose the tumor microenvironment. Moreover, extrahepatic tumors induce changes in the expression of the liver UC, which contribute to the systemic manifestations of cancer, such as weight loss. Here, we review the multilayer changes in the expression of UC enzymes throughout carcinogenesis. Understanding the changes in UC expression in the tumor and its micro and macro environment can help identify biomarkers for early cancer diagnosis and vulnerabilities that can be targeted for therapy.

Original language	English
Article number	a041538
Journal	Cold Spring Harbor perspectives in medicine
Volume	14
Issue number	4
Early online date	11 Sept 2023
DOIs	https://doi.org/10.1101/cshperspect.a041538
Publication status	Published - 1 Apr 2024

Bibliographical note

A.E. is supported by research grants from the European research program (ERC 818943), the Israel Science Foundation (860/18), and The Israel Cancer Research Fund (837124). A.E. received additional support from The Moross Integrated Cancer Center, Blumberg Family Research Fellow Chair in Honor of Talia Lynn
Steckman, from Manya and Adolph Zarovinsky, and the Koret Foundation. S.P. is funded by the Sergio Lombroso Postdoctoral Fellowship. We have a paid license to use BioRender through the Weizmann Institute.

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1101/cshperspect.a041538

Cite this

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title = "From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments",

abstract = "Catabolic pathways change in anabolic diseases such as cancer to maintain metabolic homeostasis. The liver urea cycle (UC) is the main catabolic pathway for disposing excess nitrogen. Outside the liver, the UC enzymes are differentially expressed based on each tissue's needs for UC intermediates. In tumors, there are changes in the expression of UC enzymes selected for promoting tumorigenesis by increasing the availability of essential UC substrates and products. Consequently, there are compensatory changes in the expression of UC enzymes in the cells that compose the tumor microenvironment. Moreover, extrahepatic tumors induce changes in the expression of the liver UC, which contribute to the systemic manifestations of cancer, such as weight loss. Here, we review the multilayer changes in the expression of UC enzymes throughout carcinogenesis. Understanding the changes in UC expression in the tumor and its micro and macro environment can help identify biomarkers for early cancer diagnosis and vulnerabilities that can be targeted for therapy.",

author = "Emma Hajaj and Sabina Pozzi and Ayelet Erez",

note = "A.E. is supported by research grants from the European research program (ERC 818943), the Israel Science Foundation (860/18), and The Israel Cancer Research Fund (837124). A.E. received additional support from The Moross Integrated Cancer Center, Blumberg Family Research Fellow Chair in Honor of Talia Lynn Steckman, from Manya and Adolph Zarovinsky, and the Koret Foundation. S.P. is funded by the Sergio Lombroso Postdoctoral Fellowship. We have a paid license to use BioRender through the Weizmann Institute.",

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From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments. / Hajaj, Emma; Pozzi, Sabina; Erez, Ayelet.
In: Cold Spring Harbor perspectives in medicine, Vol. 14, No. 4, a041538, 01.04.2024.

Research output: Contribution to journal › Article › peer-review

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From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments

Abstract

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