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PTEN Dual Lipid- and Protein-Phosphatase Function in Tumor Progression

SIMPLE SUMMARY: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a multifunctional tumor suppressor with protein- and lipid-phosphatase activities. The inactivation of PTEN is commonly found in all human cancers and is correlated with tumor progression. PTEN-lipid-phosphatase activ...

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Detalles Bibliográficos
Autores principales: Liu, Anne, Zhu, Yanyu, Chen, Weiping, Merlino, Glenn, Yu, Yanlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367293/
https://www.ncbi.nlm.nih.gov/pubmed/35954330
http://dx.doi.org/10.3390/cancers14153666
Descripción
Sumario:SIMPLE SUMMARY: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a multifunctional tumor suppressor with protein- and lipid-phosphatase activities. The inactivation of PTEN is commonly found in all human cancers and is correlated with tumor progression. PTEN-lipid-phosphatase activity has been well documented to dephosphorylate phosphatidylinositol-3, 4, 5-phosphate (PIP3), which hinders cell growth and survival by dampening the PI3K and AKT signaling activity. PTEN-protein-phosphatase activity is less well studied and understood. Recent studies have reported that PTEN-protein-phosphatase activity dephosphorylates the different proteins and acts in various cell functions. We here review the PTEN mutations and protein-phosphatase substrates in tumor progression. We aim to address the gap in our understanding as to how PTEN protein phosphatase contributes to its tumor-suppression functions. ABSTRACT: PTEN is the second most highly mutated tumor suppressor in cancer, following only p53. The PTEN protein functions as a phosphatase with lipid- and protein-phosphatase activity. PTEN-lipid-phosphatase activity dephosphorylates PIP3 to form PIP2, and it then antagonizes PI3K and blocks the activation of AKT, while its protein-phosphatase activity dephosphorylates different protein substrates and plays various roles in tumorigenesis. Here, we review the PTEN mutations and protein-phosphatase substrates in tumorigenesis and metastasis. Our purpose is to clarify how PTEN protein phosphatase contributes to its tumor-suppressive functions through PI3K-independent activities.