Rapid CommunicationCell Cycle Arrest by the PTEN Tumor Suppressor Is Target Cell Specific and May Require Protein Phosphatase Activity
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Cited by (45)
Synthetic Essentiality of Metabolic Regulator PDHK1 in PTEN-Deficient Cells and Cancers
2019, Cell ReportsCitation Excerpt :PTEN can also function through protein phosphatase-dependent mechanisms (Davidson et al., 2010; Gildea et al., 2004; Leslie et al., 2009; Myers et al., 1997). A growing body of literature supports biological roles for the PTEN protein phosphatase (Dey et al., 2008; Gu et al., 2011; Hlobilkova et al., 2000; Leslie et al., 2007; Shi et al., 2014; Shinde and Maddika, 2016; Tibarewal et al., 2012; Wozniak et al., 2017; You et al., 2015). The modest clinical activity of PI3K and AKT inhibitors in PTEN-deficient cancers (Chandarlapaty et al., 2011; Ghosh et al., 2013; Rodon et al., 2013) coupled with the existence of tumor-derived PTEN Y138 mutants, which specifically lack the protein phosphatase activity (Davidson et al., 2010; Tibarewal et al., 2012), suggest that protein phosphatase-dependent cellular processes may contribute to PTEN-mediated tumor suppression.
Activating PTEN Tumor Suppressor Expression with the CRISPR/dCas9 System
2019, Molecular Therapy Nucleic AcidsCitation Excerpt :CRISPR-treated SK-MEL-28 cells exhibited fewer and smaller colonies than control when grown in the presence of the B-Raf inhibitor dabrafenib, and this effect was even more pronounced for both the PI3K/mTOR inhibitor dactolisib and for the combination dabrafenib and dactolisib treatment. By dephosphorylating phosphoinositides and protein substrates on receptor tyrosine kinases and integrins, PTEN is a master regulator of downstream PI3K/AKT/mTOR- and Ras/Raf/MAPK-signaling pathways, controlling survival, motility, and drug resistance mechanisms.4–7,76 As PTEN possesses intrinsic enzymatic activity, even small changes in functional PTEN levels in cancer cells can elicit profound alterations in cancer progression.6,21,22
Quadruple Negative Breast Cancers (QNBC) Demonstrate Subtype Consistency among Primary and Recurrent or Metastatic Breast Cancer
2019, Translational OncologyCitation Excerpt :Additionally, as previously reported EGFR was elevated in AR negative TNBC tumor, which is similar to our findings [60]. PTEN, a tumor suppressor and plays role in cell cycle arrest [61,62]. PTEN is downstream of EGFR signaling [63].
PTEN expression and function in adult cancer stem cells and prospects for therapeutic targeting
2014, Advances in Biological RegulationCitation Excerpt :PTEN has also been reported to exhibit protein phosphatase activity: indeed, in vitro studies have shown that it can dephosphorylate protein substrates on serine/threonine and tyrosine residues (Leslie and Foti, 2011). PTEN protein phosphatase activity is responsible for some of its biological effects, including inhibition of cell migration and cell cycle arrest (Hlobilkova et al., 2000; Leslie and Foti, 2011). Loss of PTEN function is frequently observed in human cancer and is associated to both somatic PTEN mutations/deletions or epigenetically controlled variations in PTEN protein levels.
Inhibition of mycobacterial infection by the tumor suppressor PTEN
2012, Journal of Biological ChemistryCitation Excerpt :Importantly, we found that restoration of PTEN expression eliminated intracellular Mycoplasma and that this role was dependent on PTEN lipid phosphatase activity, as both the C124S and G129E mutants failed to do so (Fig. 3B). Recent evidence suggests that PTEN can also regulate various cellular processes with its protein phosphatase activity, although it is not clear what its physiological protein substrates are (3, 4, 21–23). Because the G129E mutant is still functional as a protein phosphatase (3), failure of the G129E mutant to suppress intracellular Mycoplasma indicates that the protein phosphatase activity of PTEN is not sufficient for this function.
- 1
Present address: Department of Pathology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
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To whom correspondence and reprint requests should be addressed. Fax: +45-35 25 77 21. E-mail: [email protected].