Journal
CANCER CELL INTERNATIONAL
Volume 23, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12935-023-02859-0
Keywords
Tumor microenvironment; Invasion; EMT; ATP internalization; Macropinocytosis; Purinergic receptor
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Despite advancements in cancer treatment, metastasis remains a major cause of cancer-related death. Epithelial-Mesenchymal Transition (EMT) plays a crucial role in cancer invasion and progression. Recent research has highlighted the importance of extracellular adenosine 5'- triphosphate (eATP) in promoting tumor growth and metastasis.
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 mu M, is 10(3)-10(4) 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.
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