TY - JOUR
T1 - Unmasking the impact of Rictor in cancer: Novel insights of mTORC2 complex
AU - Gkountakos, Anastasios
AU - Pilotto, Sara
AU - Mafficini, Andrea
AU - Vicentini, Caterina
AU - Simbolo, Michele
AU - Milella, Michele
AU - Tortora, Giampaolo
AU - Scarpa, Aldo
AU - Bria, Emilio
AU - Corbo, Vincenzo
PY - 2018
Y1 - 2018
N2 - Genomic alterations affecting components of the mechanistic target of rapamycin (mTOR) pathway are found rather frequently in cancers, suggesting that aberrant pathway activity is implicated in oncogenesis of different tumor types. mTOR functions as the core catalytic kinase of two distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which control numerous vital cellular processes. There is growing evidence indicating that Rictor, an essential subunit of the mTORC2 complex, is inappropriately overexpressed across numerous cancer types and this is associated with poor survival. To date, the candidate mechanisms responsible for aberrant Rictor expression described in cancer are two: (i) gene amplification and (ii) epigenetic regulation, mainly by microRNAs. Moreover, different mTOR-independent Rictor-containing complexes with oncogenic role have been documented, revealing alternative routes of Rictor-driven tumorigenesis, but simultaneously, paving the way for identifying novel biomarkers and therapeutic targets. Here, we review the main preclinical and clinical data regarding the role of Rictor in carcinogenesis and metastatic behavior as well as the potentiality of its alteration as a target.
AB - Genomic alterations affecting components of the mechanistic target of rapamycin (mTOR) pathway are found rather frequently in cancers, suggesting that aberrant pathway activity is implicated in oncogenesis of different tumor types. mTOR functions as the core catalytic kinase of two distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which control numerous vital cellular processes. There is growing evidence indicating that Rictor, an essential subunit of the mTORC2 complex, is inappropriately overexpressed across numerous cancer types and this is associated with poor survival. To date, the candidate mechanisms responsible for aberrant Rictor expression described in cancer are two: (i) gene amplification and (ii) epigenetic regulation, mainly by microRNAs. Moreover, different mTOR-independent Rictor-containing complexes with oncogenic role have been documented, revealing alternative routes of Rictor-driven tumorigenesis, but simultaneously, paving the way for identifying novel biomarkers and therapeutic targets. Here, we review the main preclinical and clinical data regarding the role of Rictor in carcinogenesis and metastatic behavior as well as the potentiality of its alteration as a target.
KW - Cancer Research
KW - Cancer Research
UR - https://publicatt.unicatt.it/handle/10807/133437
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85054973610&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054973610&origin=inward
U2 - 10.1093/carcin/bgy086
DO - 10.1093/carcin/bgy086
M3 - Article
SN - 0143-3334
VL - 39
SP - 971
EP - 980
JO - Carcinogenesis
JF - Carcinogenesis
IS - 8
ER -