Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43146 (
tumour suppressor
)
5,935
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The phosphoinositide 3-kinase (PI3K)/AKT signalling pathway is hyperactivated in ~70% of breast cancers. Class I PI3K generates PtdIns(3,4,5)P
3
at the plasma membrane in response to growth factor stimulation, leading to AKT activation to drive cell proliferation, survival and migration. PTEN negatively regulates PI3K/AKT signalling by dephosphorylating PtdIns(3,4,5)P
3
to form PtdIns(4,5)P
2
. PtdIns(3,4,5)P
3
can also be hydrolysed by the inositol polyphosphate 5-phosphatases (5-phosphatases) to produce PtdIns(3,4)P
2
. Interestingly, while PTEN is a bona fide
tumour suppressor
and is frequently mutated/lost in breast cancer, 5-phosphatases such as PIPP, SHIP2 and
SYNJ2
, have demonstrated more diverse roles in regulating mammary tumourigenesis. Reduced
PIPP
expression is associated with triple negative breast cancers and reduced relapse-free and overall survival. Although
PIPP
depletion enhances AKT phosphorylation and supports tumour growth, this also inhibits cell migration and metastasis in vivo, in a breast cancer oncogene-driven murine model. Paradoxically, SHIP2 and
SYNJ2
are increased in primary breast tumours, which correlates with invasive disease and reduced survival. SHIP2 or
SYNJ2
overexpression promotes breast tumourigenesis via AKT-dependent and independent mechanisms. This review will discuss how PTEN, PIPP, SHIP2 and
SYNJ2
distinctly regulate multiple functional targets, and the mechanisms by which dysregulation of these distinct phosphoinositide phosphatases differentially affect breast cancer progression.
...
PMID:PTEN and Other PtdIns(3,4,5)P
3
Lipid Phosphatases in Breast Cancer. 3327 99
