Open Access

REVIEW

Phospholipid Metabolism Reprogramming of Cancer Stem Cells and Its Impacts on Stemness

Qing Wang, Luyao Cai, Shouyi Tang, Dan Pan, Zhen Wang, Qianming Chen, Yu Zhou^*, Yingqiang Shen^*

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China

* Corresponding Authors: Yu Zhou. Email: ; Yingqiang Shen. Email:

(This article belongs to the Special Issue: Stem Cells Therapy in Health and Disease)

BIOCELL 2025, 49(4), 579-605. https://doi.org/10.32604/biocell.2025.060045

Received 22 October 2024; Accepted 31 January 2025; Issue published 30 April 2025

Abstract

Cancer Stem Cells (CSCs) are cancer cells with self-renewal and tumorigenesis abilities. CSCs in tumor tissues are the leading cause of tumor progression, recurrence, and drug resistance. CSCs have distinct metabolic features that contribute to maintaining their self-renewal and stemness. Phospholipids are essential components of cell membranes and play fundamental roles in cellular activities. CSCs have abnormal phospholipid metabolism, which affects their self-renewal, differentiation, invasion, and drug resistance. Compared with non-CSCs, the phospholipid metabolism of CSCs mainly focused on significantly increased fatty acid (FAs) and phospholipids synthesis, phospholipid unsaturation, and lipolysis-fatty acid oxidation (FAO). In brief, FA and phospholipid metabolism in the anabolic and catabolic pathways are strictly regulated in CSCs to maintain self-renewal and stemness activity. In this review, we summarize the alterations in phospholipid metabolism in CSCs and their impacts on the stemness of CSCs, and we put forward the potential applications of targeting phospholipid metabolism for CSCs, to provide directions for the development of drugs targeting the phospholipid metabolism.

---

Graphic Abstract

---

Keywords

---