PTEN Tumor-Suppressor: The Dam of Stemness in Cancer

Abstract

PTEN is one of the most frequently inactivated tumor suppressor genes in cancer. Loss or variation in PTEN gene/protein levels is commonly observed in a broad spectrum of human cancers, while germline PTEN mutations cause inherited syndromes that lead to increased risk of tumors. PTEN restrains tumorigenesis through different mechanisms ranging from phosphatase-dependent and independent activities, subcellular localization and protein interaction, modulating a broad array of cellular functions including growth, proliferation, survival, DNA repair, and cell motility. The main target of PTEN phosphatase activity is one of the most significant cell growth and pro-survival signaling pathway in cancer: PI3K/AKT/mTOR. Several shreds of evidence shed light on the critical role of PTEN in normal and cancer stem cells (CSCs) homeostasis, with its loss fostering the CSC compartment in both solid and hematologic malignancies. CSCs are responsible for tumor propagation, metastatic spread, resistance to therapy, and relapse. Thus, understanding how alterations of PTEN levels affect CSC hallmarks could be crucial for the development of successful therapeutic approaches. Here, we discuss the most significant findings on PTEN-mediated control of CSC state. We aim to unravel the role of PTEN in the regulation of key mechanisms specific for CSCs, such as self-renewal, quiescence/cell cycle, Epithelial-to-Mesenchymal-Transition (EMT), with a particular focus on PTEN-based therapy resistance mechanisms and their exploitation for novel therapeutic approaches in cancer treatment.

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

“…The PI3K/AKT/mTOR signal transduction pathway is controlled by many factors. The tumour suppressor PTEN catalyses the reaction opposite of PIP3 generation by converting PIP3 to PIP2 [66,67]. PTEN downregulates the PI3K/AKT/mTOR pathway to suppress cell proliferation and interfere with cellular metabolism, and inhibition of PTEN activity activates AKT and downstream pathways [68].…”

Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells

“…The results of this present study showed genetic alterations in 7% of patients with metastatic breast cancer in the METABRIC study ( Figure 4B). This result is supported by a recent study which demonstrated that mutation in PTEN leads to inactivation of its function as tumor suppressor genes in cancer (Luongo et al, 2019). A recent review article discussed the possibility of PTEN as a potential biomarker of lymph node metastasis of esophageal squamous cell carcinoma (Li et al, 2019b).…”

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

“…In stem cells, the presence of p53 stops cell differentiation and promotes the conversion of stem cells to progenitor cells [111]. PTEN suppresses the PI3K/Akt pathway to inhibit cell differentiation and induce cell death [112]. RECK plays a role in tumor metastasis and angiogenesis by regulating MMPs.…”