PTEN and Other PtdIns(3,4,5)P3 Lipid Phosphatases in Breast Cancer
Abstract
:1. Introduction
2. The Phosphoinositide-3-Kinase (PI3K) Signalling Pathway
2.1. AKT Isoforms
2.2. PI3K Pathway Regulation
3. PTEN
PTEN Protein Phosphatase Activity in Tumourigenesis
4. Inositol Polyphosphate 5-Phosphatases
5. The Role of PIPP in Breast Cancer Suppression
PIPP Functions as a Tumour Suppressor in Other Cancers
6. The Pro-Tumourigenic Role of SHIP2 in Breast Cancer
The Negative Role SHIP2 May Play in Cancer Progression
7. SYNJ2 Promotes Breast Tumourigenesis
8. The PtdIns(3,4,5)P3 Phosphatases in Breast Cancer: Oncogenes Versus Tumour Suppressors?
8.1. PtdIns(3,4)P2 Is An Activator of AKT Signalling
8.2. PtdIns(4,5)P2 and Cancer
9. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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PtdIns(3,4,5)P3 Phosphatase | Substrate Specificity | Cellular Localisation | Role in Breast Cancer | Mouse Models |
---|---|---|---|---|
PTEN | PtdIns(3,4,5)P3 to PtdIns(4,5)P2; PtdIns(3,4)P2 to PtdIns(4)P [48] | Plasma membrane, nucleus, ER and mitochondrial-associated membranes [84] | Tumour suppressor | Pten-null Severe developmental defects; embryonically lethal [39] Pten+/− mice de novo tumours in multiple tissues including prostate, skin, colon adrenal and mammary gland [40] Mammary epithelial cell-specific deletion of Pten Precocious lobulo-alveolar development; excessive ductal branching; high frequency of mammary tumour formation [45] |
PIPP | PtdIns(3,4,5)P3 to PtdIns(3,4)P2; PtdIns(4,5)P2 to PtdIns(4)P [77,78] | Ruffling membranes and cytosol [78] | Anti-tumourigenic; pro-migratory | Pipp-null Normal mammary gland development; no evidence of de novo mammary tumour formation [81] PyMT;Pipp−/− mice Enhanced mammary tumour formation; decreased number of lung metastases [81] |
SHIP2 | PtdIns(3,4,5)P3 to PtdIns(3,4)P2; PtdIns(4,5)P2 to PtdIns(4)P [75] | Invadopodia, focal contacts, lamellipodia, membrane ruffles [85,86,87] | Pro-tumourigenic | Ship2-null Resistant to high-fat diet induced obesity; increased insulin sensitivity and glucose tolerance [88] Transgenic overexpression Increased body weight; reduced glucose tolerance [89] |
SYNJ2 | PtdIns(3,4,5)P3 to PtdIns(3,4)P2; PtdIns(4,5)P2 to PtdIns(4)P (higher specificity for PtdIns(4,5)P2) [70] | Invadopodia, lamellipodia, membrane ruffles [83] | Pro-tumourigenic | ENU-induced mutation in catalytic domain Loss of cochlear hair cells; cochlea degeneration [90] |
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Csolle, M.P.; Ooms, L.M.; Papa, A.; Mitchell, C.A. PTEN and Other PtdIns(3,4,5)P3 Lipid Phosphatases in Breast Cancer. Int. J. Mol. Sci. 2020, 21, 9189. https://doi.org/10.3390/ijms21239189
Csolle MP, Ooms LM, Papa A, Mitchell CA. PTEN and Other PtdIns(3,4,5)P3 Lipid Phosphatases in Breast Cancer. International Journal of Molecular Sciences. 2020; 21(23):9189. https://doi.org/10.3390/ijms21239189
Chicago/Turabian StyleCsolle, Mariah P., Lisa M. Ooms, Antonella Papa, and Christina A. Mitchell. 2020. "PTEN and Other PtdIns(3,4,5)P3 Lipid Phosphatases in Breast Cancer" International Journal of Molecular Sciences 21, no. 23: 9189. https://doi.org/10.3390/ijms21239189