The regulation of PTEN: Novel insights into functions as cancer biomarkers and therapeutic targets

Abstract

This review summarizes the implications of the primary tumor suppressor protein phosphatase and tensin homolog (PTEN) in aggressive cancer development. PTEN interacts with other cellular proteins or factors suggesting the existence of an intricate molecular network that regulates their oncogenic function. Accumulating evidence has shown that PTEN exists and plays a role in the cytoplasmic organelles and in the nucleus. PTEN blocks phosphoinositide 3‐kinases (PI3K)–protein kinase B–mammalian target of rapamycin signaling pathway by dephosphorylating phosphatidylinositol (PI)‐3,4,5‐triphosphate to PI‐4,5‐bisphosphate thus counteracting PI3K function. Studies have shown that PTEN expression is tightly regulated at transcriptional, posttranscriptional, and posttranslational levels (including protein–protein interactions and posttranslational modifications). Despite recent advances in PTEN research, the regulation and function of the PTEN gene remain largely unknown. How mutation or loss of specific exons in the PTEN gene occurs and involves in cancer development is not clear. This review illustrates the regulatory mechanisms of PTEN expression and discusses how PTEN participates in tumor development and/or suppression. Future prospects for the clinical applications are also highlighted.

The ARF GTPase regulatory network in collective invasion and metastasis

“…This asymmetry is controlled by the PTEN phosphatase, which removes the 3-phosphate group from PI(3,4,5)P 3 to produce PI(4,5)P 2 [ 56 ]. PTEN is frequently perturbed — mutated, down-regulated, or lost — in cancer [ 58 ], suggesting that an imbalance in this pathway is a core part of tumourigenesis. In our recent paper, we described that PTEN-null cells become dependent on a CYTH2-ARF6-AGAP1 module to regulate active β1-integrin recycling to promote invasion [ 47 ] ( Figure 3b ).…”

PTEN Deregulation Mechanisms in Salivary Gland Carcinomas

“…consists of two distinct domains: a C2 and a protein tyrosine phosphatase that provides its enzymatic activity (11). Normally, PTEN protein catalyses inositol dephosphorylation, whereas in neoplastic and cancerous cell this function is lost (12). This biochemical reaction is significant for the inhibition of Akt signalling pathway that regulates cell survival, growth, proliferation, migration, and tissue formation (13,14).…”