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Review
. 2022 Jul 27:12:941643.
doi: 10.3389/fonc.2022.941643. eCollection 2022.

The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance

Run-Ze Li  1   2 , Xuan-Run Wang  3 , Jian Wang  4 , Chun Xie  5   6 , Xing-Xia Wang  3 , Hu-Dan Pan  1   2 , Wei-Yu Meng  3 , Tu-Liang Liang  3 , Jia-Xin Li  3 , Pei-Yu Yan  3 , Qi-Biao Wu  3 , Liang Liu  1   2 , Xiao-Jun Yao  3 , Elaine Lai-Han Leung  5   6   7
Affiliations
Review

The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance

Run-Ze Li et al. Front Oncol. .

Abstract

Biologically active sphingolipids are closely related to the growth, differentiation, aging, and apoptosis of cancer cells. Some sphingolipids, such as ceramides, are favorable metabolites in the sphingolipid metabolic pathway, usually mediating antiproliferative responses, through inhibiting cancer cell growth and migration, as well as inducing autophagy and apoptosis. However, other sphingolipids, such as S1P, play the opposite role, which induces cancer cell transformation, migration and growth and promotes drug resistance. There are also other sphingolipids, as well as enzymes, played potentially critical roles in cancer physiology and therapeutics. This review aimed to explore the important roles of sphingolipid metabolism in cancer. In this article, we summarized the role and value of sphingolipid metabolism in cancer, including the distribution of sphingolipids, the functions, and their relevance to cancer diagnosis and prognosis. We also summarized the known and potential antitumor targets present in sphingolipid metabolism, analyzed the correlation between sphingolipid metabolism and tumor immunity, and summarize the antitumor effects of natural compounds based on sphingolipids. Through the analysis and summary of sphingolipid antitumor therapeutic targets and immune correlation, we aim to provide ideas for the development of new antitumor drugs, exploration of new therapeutic means for tumors, and study of immunotherapy resistance mechanisms.

Keywords: anticancer; cancer; enzymes; immunotherapy; sphingolipid metabolism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Metabolic pathway of sphingolipids.
Figure 2
Figure 2
Nanoliposomes improve the antitumor activity of ceramides.
Figure 3
Figure 3
Influence of sphingolipids on the tumor microenvironment.
Figure 4
Figure 4
Functions of sphingolipid enzymes in the immune system.
See this image and copyright information in PMC

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