title: PTEN: Multiple Functions in Human Malignant Tumors.
abstract: PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors.
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Italia
authors.initials: I
authors.lastname: Falcone
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Conciatori
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Ursula
authors.initials: U
authors.lastname: Cesta Incani
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Anais
authors.initials: A
authors.lastname: Del Curatolo
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Inzerilli
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Carmen M A
authors.initials: CM
authors.lastname: Nuzzo
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Vanja
authors.initials: V
authors.lastname: Vaccaro
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Vari
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute , Rome , Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Ciuffreda
keywords: PHTS; PI3K; PTEN; cancer; subcellular localization