Abstract
Prostate cancer (PCa) progression involves a shift from endocrine to paracrine and eventually autocrine control resulting from alterations in molecular mechanisms in the cells. Deregulation of RNA translation is crucial for tumor cells to grow and proliferate; therefore, overactivation of the translation machinery is often observed in cancer. The two most important signal transduction pathways regulating PCa progression are PI3K/Akt/mTOR and Ras/MAPK. These two pathways converge on the eukaryotic translation initiation factor 4E (eIF4E) which binds to the protein scaffold eIF4G upon mechanistic target of rapamycin (mTOR) activation and is phosphorylated by the mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnk1/2). This review describes the role of eIF4E in mRNA translation initiation mediated by its binding to the methylated 5′ terminal structure (m7G-cap) of many mRNAs, and the ability of many tumor cells to bypass this mechanism. Hormonal therapy and chemotherapy are two of the most prevalent therapies used in patients with advanced PCa, and studies have implicated a role for eIF4E phosphorylation in promoting resistance to both these therapies. It appears that eIF4E phosphorylation enhances the rate of translation of oncogene mRNAs to increase tumorigenicity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 563-573 |
| Number of pages | 11 |
| Journal | Neoplasia (United States) |
| Volume | 20 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2018 |
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ASJC Scopus subject areas
- Cancer Research
Cite this
eIF4E Phosphorylation in Prostate Cancer. / D'Abronzo, Leandro S.; Ghosh, Paramita M.
In: Neoplasia (United States), Vol. 20, No. 6, 01.06.2018, p. 563-573.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - eIF4E Phosphorylation in Prostate Cancer
AU - D'Abronzo, Leandro S.
AU - Ghosh, Paramita M
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Prostate cancer (PCa) progression involves a shift from endocrine to paracrine and eventually autocrine control resulting from alterations in molecular mechanisms in the cells. Deregulation of RNA translation is crucial for tumor cells to grow and proliferate; therefore, overactivation of the translation machinery is often observed in cancer. The two most important signal transduction pathways regulating PCa progression are PI3K/Akt/mTOR and Ras/MAPK. These two pathways converge on the eukaryotic translation initiation factor 4E (eIF4E) which binds to the protein scaffold eIF4G upon mechanistic target of rapamycin (mTOR) activation and is phosphorylated by the mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnk1/2). This review describes the role of eIF4E in mRNA translation initiation mediated by its binding to the methylated 5′ terminal structure (m7G-cap) of many mRNAs, and the ability of many tumor cells to bypass this mechanism. Hormonal therapy and chemotherapy are two of the most prevalent therapies used in patients with advanced PCa, and studies have implicated a role for eIF4E phosphorylation in promoting resistance to both these therapies. It appears that eIF4E phosphorylation enhances the rate of translation of oncogene mRNAs to increase tumorigenicity.
AB - Prostate cancer (PCa) progression involves a shift from endocrine to paracrine and eventually autocrine control resulting from alterations in molecular mechanisms in the cells. Deregulation of RNA translation is crucial for tumor cells to grow and proliferate; therefore, overactivation of the translation machinery is often observed in cancer. The two most important signal transduction pathways regulating PCa progression are PI3K/Akt/mTOR and Ras/MAPK. These two pathways converge on the eukaryotic translation initiation factor 4E (eIF4E) which binds to the protein scaffold eIF4G upon mechanistic target of rapamycin (mTOR) activation and is phosphorylated by the mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnk1/2). This review describes the role of eIF4E in mRNA translation initiation mediated by its binding to the methylated 5′ terminal structure (m7G-cap) of many mRNAs, and the ability of many tumor cells to bypass this mechanism. Hormonal therapy and chemotherapy are two of the most prevalent therapies used in patients with advanced PCa, and studies have implicated a role for eIF4E phosphorylation in promoting resistance to both these therapies. It appears that eIF4E phosphorylation enhances the rate of translation of oncogene mRNAs to increase tumorigenicity.
UR - http://www.scopus.com/inward/record.url?scp=85046796085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046796085&partnerID=8YFLogxK
U2 - 10.1016/j.neo.2018.04.003
DO - 10.1016/j.neo.2018.04.003
M3 - Review article
C2 - 29730477
AN - SCOPUS:85046796085
VL - 20
SP - 563
EP - 573
JO - Neoplasia (United States)
JF - Neoplasia (United States)
SN - 1522-8002
IS - 6
ER -