Prostate Cancer

Pathway ID: SIGNOR-PCView in NDEx

Description: Prostate cancer (PC) is the most common male tumor. Usually is an indolent disease but about 30% of cases become aggressive; in case of metastatic cancer, about 70-80% of patients respond to androgen-deprivation therapy, but in later stages PC becomes hormone-independent and more aggressive resulting in the second cause of all male cancer deaths. PC is an heterogeneous and complex disease; it could be divided in two categories based on the presence/absence of genomic rearrangements that place proteins of the ETS transcription factor family, frequently ERG, under control of androgen responsive promoter TMPRSS2. Increased expression of ETS factors under control of AR promoter activates transcriptional program that contributes to oncogenesis by upregulating MYC and EZH2 proteins and repressing NKX3.1 ETS fusion proteins are found in 60% of PC, and the fusion-negative category could be divided into several subtype group. The most studied genomic alterations in PC affect : • the androgen receptor (AR) signalling pathway: AR plays a crucial role in the early development of PC and in its progression because of the lead role of androgen receptor transcriptional program in prostate epithelium cells. • PTEN mutations and/or deletions: PTEN is a phosphatase that acts as a tumor suppressor downregulating the PI3K-AKT signaling pathway which is essential for cell cycle progression and cell survival. • loss of function mutation of the tumor suppressor NKX3.1: this is an early event in prostate carcinogenesis. NKX3.1 and AR directly regulate each other in a loop and, together with FOXA1, are important regulators in PC progression. • point mutations in SPOP are common in primary PC. SPOP binds and promotes the degradation of SRC-3, an AR cofactor, whereas SPOP mutants lose this ability, leading to upregulated androgen signaling.

Curated by: Marta Iannuccelli

complexity level

level 1 seed interactions
level 2 connect
level 3 first neighbors
level 4 all
level 5 PPI

26 Seed Entities

Name Primary ID
AR P10275
Differentiation SIGNOR-PH37
ERG B2Y833
EZH2 Q15910
FOXA1 P55317
HDAC1 Q13547
MDM2 Q00987
Mitotic Checkpoint SIGNOR-PH28
MYC P01106
NCOA2 Q15596
NKX3-1 Q99801
PDPK1 O15530
PIK3CA P42336
PPARG P37231
Proliferation SIGNOR-PH4
PTEN P60484
PtsIns(3,4,5)P3 CID:24755492
SPOP O43791
SRD5A1 P18405
Survival SIGNOR-PH13
testosterone CID:6013
TP53 P04637
UBE2C O00762