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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
The effects of mutant Ras proteins on the cell signalome
Tamás Takács1, Gyöngyi Kudlik1, Anita Kurilla1
1Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary.
Abstract:
The genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells.
Insights
Mutant Ras proteins drive cancer progression by dysregulating key signaling pathways. This review details Ras-controlled routes, including RAF/MEK/ERK and PI3K/AKT/mTOR, and their roles in cancer stem cells.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Genetic alterations in cancer cells are linked to signaling pathway dysregulation.
- Ras proteins are key regulators of tumorigenesis, and mutations often intensify signaling networks, fueling cancer progression.
Purpose of the Study:
- To review recent studies on mutant Ras-regulated signaling routes and their cross-talk.
- To highlight the importance of Ras regulation in various signaling pathways and cancer stem cells.
Main Methods:
- Literature review of recent studies on Ras signaling in cancer.
- Analysis of Ras-driven pathways, including RAF/MEK/ERK, PI3K/AKT/mTOR, RAC/PAK, RalGDS/Ral, and PKC/PLC.
- Discussion of microRNA-regulated Ras pathways and Ras signaling in cancer stem cells.
Main Results:
- Mutant Ras intensifies multiple signaling networks, including RAF/MEK/ERK and PI3K/AKT/mTOR pathways.
- Emerging data show Ras involvement in RAC/PAK, RalGDS/Ral, and PKC/PLC signaling.
- Ras regulation by microRNAs and its role in cancer stem cells are crucial for cancer development.
Conclusions:
- Ras signaling pathways are critical in cancer progression and represent potential therapeutic targets.
- Understanding Ras cross-talk and its role in cancer stem cells is vital for developing effective cancer treatments.
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