Signaling pathways in cancer metabolism: mechanisms and therapeutic targets

Mengshu You; Zhuolin Xie; Nan Zhang; Yixuan Zhang; Desheng Xiao; Shuang Liu; Wei Zhuang; Lili Li; Yongguang Tao

doi:10.1038/s41392-023-01442-3

Signaling pathways in cancer metabolism: mechanisms and therapeutic targets

Signal Transduct Target Ther. 2023 May 10;8(1):196. doi: 10.1038/s41392-023-01442-3.

Authors

Mengshu You^#^{1

2

3}, Zhuolin Xie^#^{1

2

3}, Nan Zhang^#^{1

2

3}, Yixuan Zhang^{1

2

3}, Desheng Xiao⁴, Shuang Liu⁵, Wei Zhuang⁶, Lili Li⁷, Yongguang Tao^{8

9

10

11}

Affiliations

¹ Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410078, Changsha, Hunan, China.
² NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, 410078, Changsha, Hunan, China.
³ Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China.
⁴ Department of Pathology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
⁵ Department of Oncology, Institute of Medical Sciences, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
⁶ Department of Thoracic Surgery, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, People's Republic of China. zhuangwei@csu.edu.cn.
⁷ Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Centre for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong. lili_li@cuhk.edu.hk.
⁸ Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410078, Changsha, Hunan, China. taoyong@csu.edu.cn.
⁹ NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, 410078, Changsha, Hunan, China. taoyong@csu.edu.cn.
¹⁰ Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China. taoyong@csu.edu.cn.
¹¹ Department of Thoracic Surgery, Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer, Second Xiangya Hospital, Central South University, 410011, Changsha, China. taoyong@csu.edu.cn.

^# Contributed equally.

Abstract

A wide spectrum of metabolites (mainly, the three major nutrients and their derivatives) can be sensed by specific sensors, then trigger a series of signal transduction pathways and affect the expression levels of genes in epigenetics, which is called metabolite sensing. Life body regulates metabolism, immunity, and inflammation by metabolite sensing, coordinating the pathophysiology of the host to achieve balance with the external environment. Metabolic reprogramming in cancers cause different phenotypic characteristics of cancer cell from normal cell, including cell proliferation, migration, invasion, angiogenesis, etc. Metabolic disorders in cancer cells further create a microenvironment including many kinds of oncometabolites that are conducive to the growth of cancer, thus forming a vicious circle. At the same time, exogenous metabolites can also affect the biological behavior of tumors. Here, we discuss the metabolite sensing mechanisms of the three major nutrients and their derivatives, as well as their abnormalities in the development of various cancers, and discuss the potential therapeutic targets based on metabolite-sensing signaling pathways to prevent the progression of cancer.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Energy Metabolism
Epigenesis, Genetic
Humans
Neoplasms* / drug therapy
Neoplasms* / therapy
Signal Transduction
Tumor Microenvironment