The Role of Wild-Type RAS in Oncogenic RAS Transformation

The family of oncogenes ( , , and ) are among the most frequently mutated protein families in cancers. -mutated tumors were originally thought to proliferate independently of upstream signaling inputs, but we now know that non-mutated wild-type (WT) RAS proteins play an important role in modulating...

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Bibliographic Details
Published in:Genes 2021-04, Vol.12 (5), p.662
Main Authors: Sheffels, Erin, Kortum, Robert L
Format: Article
Language:English
Subjects:
Apoptosis
Cancer therapies
Cell proliferation
Colorectal cancer
Endometrial cancer
Genes
Genetic transformation
Lung cancer
Medical prognosis
Metastasis
Mutation
Pancreatic cancer
Protein families
Proteins
Ras protein
Review
Tumorigenesis
Tumors
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Summary:The family of oncogenes ( , , and ) are among the most frequently mutated protein families in cancers. -mutated tumors were originally thought to proliferate independently of upstream signaling inputs, but we now know that non-mutated wild-type (WT) RAS proteins play an important role in modulating downstream effector signaling and driving therapeutic resistance in -mutated cancers. This modulation is complex as different WT RAS family members have opposing functions. The protein product of the allele of the same isoform as mutated is often tumor-suppressive and lost during tumor progression. In contrast, RTK-dependent activation of the WT RAS proteins from the two non-mutated WT family members is tumor-promoting. Further, rebound activation of RTK-WT RAS signaling underlies therapeutic resistance to targeted therapeutics in -mutated cancers. The contributions of WT RAS to proliferation and transformation in -mutated cancer cells places renewed interest in upstream signaling molecules, including the phosphatase/adaptor SHP2 and the RasGEFs SOS1 and SOS2, as potential therapeutic targets in -mutated cancers.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes12050662