RAS-mediated oncogenic signaling pathways in human malignancies
Abdul Q Khan1, Shilpa Kuttikrishnan1, Kodappully S Siveen1
1Academic Health System, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar.
Abstract:
Abnormally activated RAS proteins are the main oncogenic driver that governs the functioning of major signaling pathways involved in the initiation and development of human malignancies. Mutations in RAS genes and or its regulators, most frequent in human cancers, are the main force for incessant RAS activation and associated pathological conditions including cancer. In general, RAS is the main upstream regulator of the highly conserved signaling mechanisms associated with a plethora of important cellular activities vital for normal homeostasis. Mutated or the oncogenic RAS aberrantly activates a web of interconnected signaling pathways including RAF-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase), phosphoinositide-3 kinase (PI3K)/AKT (protein kinase B), protein kinase C (PKC) and ral guanine nucleotide dissociation stimulator (RALGDS), etc., leading to uncontrolled transcriptional expression and reprogramming in the functioning of a range of nuclear and cytosolic effectors critically associated with the hallmarks of carcinogenesis. This review highlights the recent literature on how oncogenic RAS negatively use its signaling web in deregulating the expression and functioning of various effector molecules in the pathogenesis of human malignancies.
Insights
Abnormally activated RAS proteins drive human cancer by hijacking key cell signaling pathways. This review explores how oncogenic RAS dysregulates effector molecules, promoting carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Abnormal RAS protein activation is a primary driver of human malignancies.
- RAS mutations are frequent in cancers, leading to sustained pathway activation.
- RAS regulates critical cellular activities essential for homeostasis.
Purpose of the Study:
- To review recent literature on oncogenic RAS signaling.
- To elucidate how RAS dysregulates effector molecules in cancer pathogenesis.
- To highlight the role of RAS in reprogramming cellular functions.
Main Methods:
- Literature review of recent scientific publications.
- Analysis of signaling pathways regulated by RAS.
- Examination of effector molecule expression and function.
Main Results:
- Oncogenic RAS aberrantly activates interconnected signaling pathways (e.g., RAF-MEK-ERK, PI3K/AKT).
- RAS signaling reprogramming leads to uncontrolled transcriptional changes.
- Dysregulated effector molecules contribute to the hallmarks of carcinogenesis.
Conclusions:
- Oncogenic RAS utilizes its signaling network to promote cancer development.
- Understanding RAS signaling is crucial for targeting cancer pathogenesis.
- RAS-driven deregulation of effectors is a key mechanism in malignancy.
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