Extracellular Phosphatidic Acid: A Novel Regulator of Lung Cancer Cell Migration – Role of the PI3K/AKT Pathway
<p>Lung cancer is one of the most lethal types of cancer, being responsible for the majority of cancer-associated deaths worldwide. The main therapeutic strategy for the treatment of lung cancer is chemotherapy, but the currently available drugs are not sufficiently effective to overcome the disease...
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| Autores principales: | , , , , , |
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| Formato: | Capítulo de libro |
| Lenguaje: | inglés |
| Publicado: |
IntechOpen
2026
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| Materias: | |
| Acceso en línea: | https://www.intechopen.com/chapters/1237807 |
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| Sumario: | <p>Lung cancer is one of the most lethal types of cancer, being responsible for the majority of cancer-associated deaths worldwide. The main therapeutic strategy for the treatment of lung cancer is chemotherapy, but the currently available drugs are not sufficiently effective to overcome the disease. In the present chapter, we show that extracellular phosphatidic acid (PA), a bioactive phospholipid involved in inflammatory responses and cell proliferation, induces rapid phosphorylation of AKT and mammalian target of rapamycin (mTOR), and that pretreatment of the cells with LY294002, 10-DEBC, or rapamycin, which specifically inhibit phosphatidylinositol 3-kinase (PI3K), AKT, or mTOR, respectively, blocks PA-stimulated lung cancer cell migration. Additionally, AM966 and Ki16425, which inhibit lysophosphatidic acid receptor 1 (LPAR1), completely block PA-stimulated phosphorylation of mTOR and lung cancer cell migration, suggesting that stimulation of chemotaxis by PA involves its interaction with LPA receptors. Moreover, exogenous PA induced phosphorylation of focal adhesion kinase (FAK), which is upstream of Rac1 activation, and inhibition of FAK or Rac1 also blocked PA-stimulated lung cancer cell migration. It can be concluded that the PA-LPA1-PI3K-AKT-mTOR pathway and the FAK/Rac1 axis are highly relevant factors for regulation of lung cancer cell migration, and that inhibition of PA generation may be of crucial importance for reducing lung cancer dissemination.</p> |
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| ISBN: | 978-1-80631-682-3 |
| DOI: | 10.5772/intechopen.1014164 |