An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential

Cancer Cell International

Review

Xuan Wang¹  Haiyun Zhang¹  Yanyang Cao¹  Jingwen Song¹  Xiaozhuo Chen²  Eileen Chen³ 

[1] Department of Biological Sciences, Ohio University, Athens, OH, USA;Interdisciplinary Graduate Program in Molecular and Cellular Biology, Ohio University, Athens, OH, USA;The Edison Biotechnology Institute, Ohio University, Athens, OH, USA;Department of Biological Sciences, Ohio University, Athens, OH, USA;Interdisciplinary Graduate Program in Molecular and Cellular Biology, Ohio University, Athens, OH, USA;The Edison Biotechnology Institute, Ohio University, Athens, OH, USA;Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USA;Heritage College of Osteopathic Medicine, Ohio University, 45701, Athens, OH, USA;Heritage College of Osteopathic Medicine, Ohio University, 45701, Athens, OH, USA;

关键词: Tumor microenvironment;    Invasion;    EMT;    ATP internalization;    Macropinocytosis;    Purinergic receptor;   

DOI  :  10.1186/s12935-023-02859-0

 received in 2022-11-13, accepted in 2023-01-24,  发布年份 2023

来源: Springer

【 摘 要 】

Despite the rapid development of therapeutic strategies in cancer treatment, metastasis remains the major cause of cancer-related death and scientific challenge. Epithelial-Mesenchymal Transition (EMT) plays a crucial role in cancer invasion and progression, a process by which tumor cells lose cell-cell adhesion and acquire increased invasiveness and metastatic activity. Recent work has uncovered some crucial roles of extracellular adenosine 5’- triphosphate (eATP), a major component of the tumor microenvironment (TME), in promoting tumor growth and metastasis. Intratumoral extracellular ATP (eATP), at levels of 100–700 µM, is 103–104 times higher than in normal tissues. In the current literature, eATP’s function in promoting metastasis has been relatively poorly understood as compared with intracellular ATP (iATP). Recent evidence has shown that cancer cells internalize eATP via macropinocytosis in vitro and in vivo, promoting cell growth and survival, drug resistance, and metastasis. Furthermore, ATP acts as a messenger molecule that activates P2 purinergic receptors expressed on both tumor and host cells, stimulating downstream signaling pathways to enhance the invasive and metastatic properties of tumor cells. Here, we review recent progress in understanding eATP’s role in each step of the metastatic cascade, including initiating invasion, inducing EMT, overcoming anoikis, facilitating intravasation, circulation, and extravasation, and eventually establishing metastatic colonization. Collectively, these studies reveal eATP’s important functions in many steps of metastasis and identify new opportunities for developing more effective therapeutic strategies to target ATP-associated processes in cancer.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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