The PI3K-AKT-mTOR Pathway and Prostate Cancer: at the Crossroads of AR, MAPK, and WNT Signaling
Oncogenic activation of the phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathway is a frequent event in prostate cancer that facilitates tumor formation, disease progression and therapeutic resistance. Recent discoveries indicate that the...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-06-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/12/4507 |
id |
doaj-a980eacb31324e33bfab82ff939ebdfb |
---|---|
record_format |
Article |
spelling |
doaj-a980eacb31324e33bfab82ff939ebdfb2020-11-25T03:08:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-01214507450710.3390/ijms21124507The PI3K-AKT-mTOR Pathway and Prostate Cancer: at the Crossroads of AR, MAPK, and WNT SignalingBoris Y. Shorning0Manisha S. Dass1Matthew J. Smalley2Helen B. Pearson3The European Cancer Stem Cell Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, Wales, UKThe European Cancer Stem Cell Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, Wales, UKThe European Cancer Stem Cell Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, Wales, UKThe European Cancer Stem Cell Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, Wales, UKOncogenic activation of the phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathway is a frequent event in prostate cancer that facilitates tumor formation, disease progression and therapeutic resistance. Recent discoveries indicate that the complex crosstalk between the PI3K-AKT-mTOR pathway and multiple interacting cell signaling cascades can further promote prostate cancer progression and influence the sensitivity of prostate cancer cells to PI3K-AKT-mTOR-targeted therapies being explored in the clinic, as well as standard treatment approaches such as androgen-deprivation therapy (ADT). However, the full extent of the PI3K-AKT-mTOR signaling network during prostate tumorigenesis, invasive progression and disease recurrence remains to be determined. In this review, we outline the emerging diversity of the genetic alterations that lead to activated PI3K-AKT-mTOR signaling in prostate cancer, and discuss new mechanistic insights into the interplay between the PI3K-AKT-mTOR pathway and several key interacting oncogenic signaling cascades that can cooperate to facilitate prostate cancer growth and drug-resistance, specifically the androgen receptor (AR), mitogen-activated protein kinase (MAPK), and WNT signaling cascades. Ultimately, deepening our understanding of the broader PI3K-AKT-mTOR signaling network is crucial to aid patient stratification for PI3K-AKT-mTOR pathway-directed therapies, and to discover new therapeutic approaches for prostate cancer that improve patient outcome.https://www.mdpi.com/1422-0067/21/12/4507AKTARcastration-resistant prostate cancer (CRPC)MAPKmTORPI3K |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Boris Y. Shorning Manisha S. Dass Matthew J. Smalley Helen B. Pearson |
spellingShingle |
Boris Y. Shorning Manisha S. Dass Matthew J. Smalley Helen B. Pearson The PI3K-AKT-mTOR Pathway and Prostate Cancer: at the Crossroads of AR, MAPK, and WNT Signaling International Journal of Molecular Sciences AKT AR castration-resistant prostate cancer (CRPC) MAPK mTOR PI3K |
author_facet |
Boris Y. Shorning Manisha S. Dass Matthew J. Smalley Helen B. Pearson |
author_sort |
Boris Y. Shorning |
title |
The PI3K-AKT-mTOR Pathway and Prostate Cancer: at the Crossroads of AR, MAPK, and WNT Signaling |
title_short |
The PI3K-AKT-mTOR Pathway and Prostate Cancer: at the Crossroads of AR, MAPK, and WNT Signaling |
title_full |
The PI3K-AKT-mTOR Pathway and Prostate Cancer: at the Crossroads of AR, MAPK, and WNT Signaling |
title_fullStr |
The PI3K-AKT-mTOR Pathway and Prostate Cancer: at the Crossroads of AR, MAPK, and WNT Signaling |
title_full_unstemmed |
The PI3K-AKT-mTOR Pathway and Prostate Cancer: at the Crossroads of AR, MAPK, and WNT Signaling |
title_sort |
pi3k-akt-mtor pathway and prostate cancer: at the crossroads of ar, mapk, and wnt signaling |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-06-01 |
description |
Oncogenic activation of the phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathway is a frequent event in prostate cancer that facilitates tumor formation, disease progression and therapeutic resistance. Recent discoveries indicate that the complex crosstalk between the PI3K-AKT-mTOR pathway and multiple interacting cell signaling cascades can further promote prostate cancer progression and influence the sensitivity of prostate cancer cells to PI3K-AKT-mTOR-targeted therapies being explored in the clinic, as well as standard treatment approaches such as androgen-deprivation therapy (ADT). However, the full extent of the PI3K-AKT-mTOR signaling network during prostate tumorigenesis, invasive progression and disease recurrence remains to be determined. In this review, we outline the emerging diversity of the genetic alterations that lead to activated PI3K-AKT-mTOR signaling in prostate cancer, and discuss new mechanistic insights into the interplay between the PI3K-AKT-mTOR pathway and several key interacting oncogenic signaling cascades that can cooperate to facilitate prostate cancer growth and drug-resistance, specifically the androgen receptor (AR), mitogen-activated protein kinase (MAPK), and WNT signaling cascades. Ultimately, deepening our understanding of the broader PI3K-AKT-mTOR signaling network is crucial to aid patient stratification for PI3K-AKT-mTOR pathway-directed therapies, and to discover new therapeutic approaches for prostate cancer that improve patient outcome. |
topic |
AKT AR castration-resistant prostate cancer (CRPC) MAPK mTOR PI3K |
url |
https://www.mdpi.com/1422-0067/21/12/4507 |
work_keys_str_mv |
AT borisyshorning thepi3kaktmtorpathwayandprostatecanceratthecrossroadsofarmapkandwntsignaling AT manishasdass thepi3kaktmtorpathwayandprostatecanceratthecrossroadsofarmapkandwntsignaling AT matthewjsmalley thepi3kaktmtorpathwayandprostatecanceratthecrossroadsofarmapkandwntsignaling AT helenbpearson thepi3kaktmtorpathwayandprostatecanceratthecrossroadsofarmapkandwntsignaling AT borisyshorning pi3kaktmtorpathwayandprostatecanceratthecrossroadsofarmapkandwntsignaling AT manishasdass pi3kaktmtorpathwayandprostatecanceratthecrossroadsofarmapkandwntsignaling AT matthewjsmalley pi3kaktmtorpathwayandprostatecanceratthecrossroadsofarmapkandwntsignaling AT helenbpearson pi3kaktmtorpathwayandprostatecanceratthecrossroadsofarmapkandwntsignaling |
_version_ |
1724665289353723904 |