An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential
Abstract 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 l...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-023-02859-0 |
| _version_ | 1811165722382958592 |
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| author | Yanyang Cao Eileen Chen Xuan Wang Jingwen Song Haiyun Zhang Xiaozhuo Chen |
| author_facet | Yanyang Cao Eileen Chen Xuan Wang Jingwen Song Haiyun Zhang Xiaozhuo Chen |
| author_sort | Yanyang Cao |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T15:41:17Z |
| format | Article |
| id | doaj.art-b562a2f892684208b410e97c06458967 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-10T15:41:17Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-b562a2f892684208b410e97c064589672023-02-12T12:23:24ZengBMCCancer Cell International1475-28672023-02-0123111610.1186/s12935-023-02859-0An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potentialYanyang Cao0Eileen Chen1Xuan Wang2Jingwen Song3Haiyun Zhang4Xiaozhuo Chen5Department of Biological Sciences, Ohio UniversityHeritage College of Osteopathic Medicine, Ohio UniversityDepartment of Biological Sciences, Ohio UniversityDepartment of Biological Sciences, Ohio UniversityDepartment of Biological Sciences, Ohio UniversityDepartment of Biological Sciences, Ohio UniversityAbstract 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.https://doi.org/10.1186/s12935-023-02859-0Tumor microenvironmentInvasionEMTATP internalizationMacropinocytosisPurinergic receptor |
| spellingShingle | Yanyang Cao Eileen Chen Xuan Wang Jingwen Song Haiyun Zhang Xiaozhuo Chen 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 Tumor microenvironment Invasion EMT ATP internalization Macropinocytosis Purinergic receptor |
| title | An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential |
| title_full | An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential |
| title_fullStr | An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential |
| title_full_unstemmed | An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential |
| title_short | An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential |
| title_sort | emerging master inducer and regulator for epithelial mesenchymal transition and tumor metastasis extracellular and intracellular atp and its molecular functions and therapeutic potential |
| topic | Tumor microenvironment Invasion EMT ATP internalization Macropinocytosis Purinergic receptor |
| url | https://doi.org/10.1186/s12935-023-02859-0 |
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