gRASping the redox lever to modulate cancer cell fate signaling
MetadataShow full item record
© 2019 The Authors RAS proteins are critical regulators of signaling networks controlling diverse cellular functions such as cell proliferation and survival and its mutation are among the most powerful oncogenic drivers in human cancers. Despite intense efforts, direct RAS-targeting strategies remain elusive due to its “undruggable” nature. To that end, bulk of the research efforts has been directed towards targeting upstream and/or downstream of RAS signaling. However, the therapeutic efficacies of these treatments are limited in the long run due to the acquired drug resistance in RAS-driven cancers. Interestingly, recent studies have uncovered a potential role of RAS in redox-regulation as well as the interplay between ROS and RAS-associated signaling networks during process of cancer initiation and progression. More specifically, these studies provide ample evidence to implicate RAS as a redox-rheostat, manipulating ROS levels to provide a redox-milieu conducive for carcinogenesis. Importantly, the understanding of RAS-ROS interplay could provide us with novel targetable vulnerabilities for designing therapeutic strategies. In this review, we provide a brief summary of the advances in the field to illustrate the dual role of RAS in redox-regulation and its implications in RAS signaling outcomes and also emerging redox-based strategies to target RAS-driven cancers.
Showing items related by title, author, creator and subject.
Chong, S.; Lai, J.; Eu, J.; Bellot, G.; Pervaiz, Shazib (2018)© 2018, Mary Ann Liebert, Inc., publishers. Significance: There is evidence to implicate reactive oxygen species (ROS) in tumorigenesis and its progression. This has been associated with the interplay between ROS and ...
Pohl, Sebastian; Agostino, Mark; Dharmarajan, Arunasalam; Pervaiz, Shazib (2018)SIGNIFICANCE B cell lymphoma-2 (Bcl-2) is the prototypical anti-apoptotic member of the Bcl-2 family that comprises proteins with contrasting effects on cell fate. Identified as a consequence chromosomal translocation (t ...
Mechanism of the induction of endoplasmic reticulum stress by the anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT): Activation of PERK/eIF2a, IRE1a, ATF6 and calmodulin kinaseMerlot, A.; Shafie, N.; Yu, Yu; Richardson, V.; Jansson, P.; Sahni, S.; Lane, D.; Kovacevic, Z.; Kalinowski, D.; Richardson, D. (2016)The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca2+) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins ...