TY - JOUR
T1 - Contextual signaling in cancer
AU - Smithson, Laura J.
AU - Anastasaki, Corina
AU - Chen, Ran
AU - Toonen, Joseph A.
AU - Williams, Sidney B.
AU - Gutmann, David H.
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/10/1
Y1 - 2016/10/1
N2 - The formation and maintenance of an organism are highly dependent on the orderly control of cell growth, differentiation, death, and migration. These processes are tightly regulated by signaling cascades in which a limited number of molecules dictate these cellular events. While these signaling pathways are highly conserved across species and cell types, the functional outcomes that result from their engagement are specified by the context in which they are activated. Using the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome as an illustrative platform, we discuss how NF1/RAS signaling can create functional diversity at multiple levels (molecular, cellular, tissue, and genetic/genomic). As such, the ability of related molecules (e.g., K-RAS, H-RAS) to activate distinct effectors, as well as cell type- and tissue-specific differences in molecular composition and effector engagement, generate numerous unique functional effects. These variations, coupled with a multitude of extracellular cues and genomic/genetic changes that each modify the innate signaling properties of the cell, enable precise control of cellular physiology in both health and disease. Understanding these contextual influences is important when trying to dissect the underlying pathogenic mechanisms of cancer relevant to molecularly-targeted therapeutics.
AB - The formation and maintenance of an organism are highly dependent on the orderly control of cell growth, differentiation, death, and migration. These processes are tightly regulated by signaling cascades in which a limited number of molecules dictate these cellular events. While these signaling pathways are highly conserved across species and cell types, the functional outcomes that result from their engagement are specified by the context in which they are activated. Using the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome as an illustrative platform, we discuss how NF1/RAS signaling can create functional diversity at multiple levels (molecular, cellular, tissue, and genetic/genomic). As such, the ability of related molecules (e.g., K-RAS, H-RAS) to activate distinct effectors, as well as cell type- and tissue-specific differences in molecular composition and effector engagement, generate numerous unique functional effects. These variations, coupled with a multitude of extracellular cues and genomic/genetic changes that each modify the innate signaling properties of the cell, enable precise control of cellular physiology in both health and disease. Understanding these contextual influences is important when trying to dissect the underlying pathogenic mechanisms of cancer relevant to molecularly-targeted therapeutics.
KW - Astrocyte
KW - Glioma
KW - NF1
KW - Nervous system
KW - Neuron
KW - RAS
KW - mTOR
UR - http://www.scopus.com/inward/record.url?scp=84991107087&partnerID=8YFLogxK
U2 - 10.1016/j.semcdb.2016.06.002
DO - 10.1016/j.semcdb.2016.06.002
M3 - Review article
C2 - 27269372
AN - SCOPUS:84991107087
SN - 1084-9521
VL - 58
SP - 118
EP - 126
JO - Seminars in Cell and Developmental Biology
JF - Seminars in Cell and Developmental Biology
ER -