The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic
| Autor: | Cynthia Lopez-Haber, Mariana Cooke, Martin J. Baker, María J. Caloca, Shaofei Wang, Victoria Casado-Medrano, Marcelo G. Kazanietz |
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| Přispěvatelé: | National Institutes of Health (US) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tumour susceptibility RAC1 Biology medicine.disease_cause Biochemistry Article Metastasis 03 medical and health sciences Neoplasms Rho GTPases medicine Humans Receptor Rac–GEF Effector Cancer medicine.disease Phenotype rac GTP-Binding Proteins Rac 030104 developmental biology Disease Progression Cancer signaling Disease Susceptibility Guanine nucleotide exchange factor Carcinogenesis Cancer therapeutics Signal Transduction |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | The family of Rho GTPases are involved in the dynamic control of cytoskeleton reorganization and other fundamental cellular functions, including growth, motility, and survival. Rac1, one of the best characterized Rho GTPases, is an established effector of receptors and an important node in signaling networks crucial for tumorigenesis and metastasis. Rac1 hyperactivation is common in human cancer and could be the consequence of overexpression, abnormal upstream inputs, deregulated degradation, and/or anomalous intracellular localization. More recently, cancer-associated gain-of-function mutations in Rac1 have been identified which contribute to tumor phenotypes and confer resistance to targeted therapies. Deregulated expression/activity of Rac guanine nucleotide exchange factors responsible for Rac activation has been largely associated with a metastatic phenotype and drug resistance. Translating our extensive knowledge in Rac pathway biochemistry into a clinical setting still remains a major challenge; nonetheless, remarkable opportunities for cancer therapeutics arise from promising lead compounds targeting Rac and its effectors. M.G.K.’s laboratory is supported by grants R01-CA189765, R01-CA196232, and R01-ES026023 from the National Institutes of Health (NIH). |
| Databáze: | OpenAIRE |
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