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...

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Main Authors: Boris Y. Shorning, Manisha S. Dass, Matthew J. Smalley, Helen B. Pearson
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:International Journal of Molecular Sciences
Subjects:
AKT
AR
Online Access:https://www.mdpi.com/1422-0067/21/12/4507
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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
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