PTEN: Multiple functions in human malignant tumors

Michele Milella, Italia Falcone, Fabiana Conciatori, Ursula Cesta Incani, Anais Del Curatolo, Nicola Inzerilli, Carmen M A Nuzzo, Vanja Vaccaro, Sabrina Vari, Francesco Cognetti, Ludovica Ciuffreda

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number024
JournalFrontiers in Oncology
Volume5
Issue numberFEB
DOIs
Publication statusPublished - 2015

Keywords

  • Cancer
  • PHTS
  • PIK
  • PTEN
  • Subcellular localization

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Milella, M., Falcone, I., Conciatori, F., Incani, U. C., Del Curatolo, A., Inzerilli, N., Nuzzo, C. M. A., Vaccaro, V., Vari, S., Cognetti, F., & Ciuffreda, L. (2015). PTEN: Multiple functions in human malignant tumors. Frontiers in Oncology, 5(FEB), [024]. https://doi.org/10.3389/fonc.2015.00024