Ras-ling with new therapeutic targets for metastasis
| Autor: | Zachary T. Schafer, Joshua A. Mason |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAP Kinase Signaling System Antineoplastic Agents Protein Serine-Threonine Kinases Biology Biochemistry Immediate-Early Proteins Metastasis Extracellular matrix 03 medical and health sciences Anti-apoptotic Ras signalling cascade medicine Humans Anoikis Molecular Targeted Therapy Neoplasm Metastasis Oncogene Effector Cell Biology medicine.disease Extracellular Matrix Cell biology 030104 developmental biology Mutation Cancer cell ras Proteins SGK1 Commentary - Commissioned Signal Transduction |
| Zdroj: | Small GTPases. :1-5 |
| ISSN: | 2154-1256 2154-1248 |
| DOI: | 10.1080/21541248.2017.1310650 |
| Popis: | Successful cancer metastasis relies on the ability of cancer cells to survive independently of attachment to the extracellular matrix (ECM) and to overcome ECM-detachment-induced death programs. This can be accomplished through activating mutations in cellular oncogenes that subsequently lead to the inhibition of anoikis and to alterations in productive metabolism. One example of such an oncogene is Ras which is found to be mutated and hyperactivated in a variety of distinct cancers. Despite numerous studies on Ras, the precise molecular mechanisms that facilitate survival during ECM-detachment remain poorly understood. Recently, we discovered that ECM-detached cells harboring oncogenic Ras mutations require signaling through the PI(3)K/SGK1 signaling axis to promote survival. Furthermore, we found that oncogenic Ras can concurrently diminish PHLPP1 phosphatase levels, which results in a decrease in p38 MAPK-mediated activation of anoikis. Thus, our data suggest that cancer cells with activating Ras mutations can survive during ECM-detachment using downstream effector molecules that modulate distinct pathways. Overall, these data suggest that new therapeutic interventions that aim to mitigate SGK1 signaling and activate the p38 MAPK activity may aid in specifically targeting and eliminating metastatic cancer cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|