PTEN
Phosphatase that erases PIP3 and so shuts down the PI3K arm. One of the most frequently lost tumour suppressors in human cancer, and one of the most common ways this pathway is left switched on without its growth-factor brake.
Erases the signal PI3K writes. A tumor-suppressing enzyme that erases the 'go' signal generated by PI3K, shutting that branch of the pathway down. It's one of the genes most frequently lost in human cancer, and losing it is one of the most common ways this pathway is left switched on without its growth-factor brake.
PTEN does not inhibit the PI3K enzyme; it dephosphorylates PI3K's product, PIP3. Haploinsufficient tumour suppressor with dose-dependent phenotypes.
TL;DR. PTEN appears in 4 curated studies in Oliver's mTOR Atlas: 3 in animal models; 1 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| PTEN inhibits PI3K mechanism: functional-consequence · this link in full · on the map table | PTEN erases the lipid signal that PI3K makes. Losing PTEN is one of the most common ways cancers keep this whole pathway switched on without any signal from outside. PTEN erases PIP3, undoing PI3K. Losing PTEN is one of the commonest ways a tumour leaves this whole axis switched on without an upstream signal. PTEN erases PIP3, undoing PI3K. Losing PTEN is one of the commonest ways a tumour leaves this whole axis switched on without an upstream signal. Holds under: The arrow is drawn PTEN -> PI3K for readability, but PTEN does not act on the PI3K enzyme. It dephosphorylates PIP3, PI3K's lipid product, so the effect on PI3K signalling is indirect and the edge is a compressed one whose hidden intermediate is PIP3. The canonical biochemical demonstration (Maehama & Dixon, J Biol Chem 1998, PMID 9593664) sits outside this corpus: purified recombinant PTEN dephosphorylates PtdIns(3,4,5)P3 specifically at position 3, and in the same paper PTEN overexpression reduced insulin-induced PIP3 without affecting insulin-induced PI3K activation. The cancer-genetics support in-corpus is mouse (GUE2009). The 'inhibits' label describes the net effect on signalling, not the enzyme itself: PTEN does not inhibit PI3K catalytically, and Maehama & Dixon reported PI3K activation itself unchanged. PTEN dephosphorylates PIP3, PI3K's lipid product, erasing the signal downstream of the enzyme rather than blocking the enzyme's activity. plausible in people, not shown directly · settled in the literature | A | GUE2009 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 3 |
| M | Molecular — cells, biochemistry, structure | 1 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2009 | A | mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice GUE2009 mTORC2 is required for prostate cancer driven by Pten loss in mice. |
| 2009 | A | Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice ZHO2009 In neural Pten-knockout mice, rapamycin prevented and reversed neuronal hypertrophy and improved a subset of the PTEN-associated abnormal behaviours. |
| 2004 | A | mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways MAJ2004 mTOR inhibition (rapamycin/RAD001) reverses Akt-driven prostate intraepithelial neoplasia in mice. |
| 2026 | M | PTEN regulates microtubule polymerization via mTORC2, but not mTORC1, in peripheral sensory neurons EVA2026 Uses Raptor (mTORC1) versus Rictor (mTORC2) co-deletion on a Pten-knockout background to ask which complex carries the growth signal to the microtubule cytoskeleton. Suppressing mTORC2 — but not mTORC1 — returns the accelerated microtubule polymerisation and neuronal hypertrophy of Pten-KO neurons to wild-type levels, and the effect is confined to the axonal growth cone rather than the proximal axon shaft. A clean genetic dissection on the comparatively thin mTORC2 side of the pathway. |
Related entities
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