PTEN secretion in exosomes

Putz, Ulrich; Mah, Sophia; Goh, Choo-Peng; Low, Ley-Hian; Howitt, Jason; Tan, Seong‐Seng

doi:10.1016/j.ymeth.2014.12.016

Cited by 21 publications

(17 citation statements)

References 29 publications

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“…4b ). Recently, a few studies have suggested that active PTEN may be secreted and taken up by neighboring cells 35 – 37 . With high transient expression of PTEN in transfected cells, some functional PTEN may be exported into the supernatant and taken up by the surrounding cells that have not been transfected.…”

Section: Resultsmentioning

confidence: 99%

PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer

Wozniak¹,

Kajdacsy-Balla

Macias

et al. 2017

Nat Commun

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PTEN activity is often lost in prostate cancer. We show that the tyrosine kinase PTK6 (BRK) is a PTEN substrate. Phosphorylation of PTK6 tyrosine 342 (PY342) promotes activation, while phosphorylation of tyrosine 447 (PY447) regulates auto-inhibition. Introduction of PTEN into a PTEN null prostate cancer cell line leads to dephosphorylation of PY342 but not PY447 and PTK6 inhibition. Conversely, PTEN knockdown promotes PTK6 activation in PTEN positive cells. Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342. Conditional disruption of Pten in the mouse prostate leads to tumorigenesis and increased phosphorylation of PTK6 Y342, and disruption of Ptk6 impairs tumorigenesis. In human prostate tumor tissue microarrays, loss of PTEN correlates with increased PTK6 PY342 and poor outcome. These data suggest PTK6 activation promotes invasive prostate cancer induced by PTEN loss.

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Section: Resultsmentioning

confidence: 99%

PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer

Wozniak¹,

Kajdacsy-Balla

Macias

et al. 2017

Nat Commun

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“…TEX also modulate various cellular and intercellular signaling pathways that are implicated in cancer promotion, such as the TGF-β, the Wnt-β-catenin and the Notch pathways [63,64,67] and the pro-tumorigenic effects of TEX seem to predominate in the tumor microenvironment. Exosome secretion by tumor cells was found to be regulated by the p53 protein [68] and PTEN, which regulates the PI3K-AKT signaling, was found to be carried in TEX and to mediate phosphatase activity in recipient cells [69,70]. These examples indicate that tumor cells utilize exosomal signaling as a major aspect of pro-tumorigenic intracellular communication.…”

Section: Definition Biogenesis and Characteristics Of Exosomesmentioning

confidence: 99%

The potential of tumor-derived exosomes for noninvasive cancer monitoring

Whiteside

2015

Expert Review of Molecular Diagnostics

123

108

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Tumor-derived exosomes (TEXs) are emerging as a new type of cancer biomarker. TEXs are membrane-bound, virus-size vesicles of endocytic origin present in all body fluids of cancer patients. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by tumor cells and cancer cell-specific molecular and genetic contents, TEXs are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of tumor cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma of cancer patients responding to therapies appear to correlate with clinical endpoints. However, methods for TEX isolation and separation from the bulk of human plasma-derived exosomes are not yet established and their role as biomarkers remains to be confirmed. Further development and validation of TEXs as noninvasive, liquid equivalents of tumor biopsies are necessary to move this effort forward.

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“…One study has demonstrated that PTEN is exported into exosomes and accepted by recipient cells, in which PTEN exhibits phosphatase activity. 28,29 However, we did not observe the antiviral activity when we treated cells with the culture supernatant of PTEN-expressing cells (Figure 4). This result might be tentatively explained as follows.…”

Section: Discussionmentioning

confidence: 81%

PTEN-L promotes type I interferon responses and antiviral immunity

et al. 2017

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Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a well-known tumor suppressor that acts as a dual-specificity phosphatase and is frequently mutated in human cancer. Our previous work has demonstrated that PTEN also plays a vital role in type I interferon responses and antiviral innate immunity. Recently, a translational variant of PTEN with a long N-terminal extension (PTEN-L) has been discovered that is secreted into the extracellular environment and enters recipient cells, where it exerts a phosphatase function antagonistic to PI3K/Akt signaling and tumorigenesis. In this study, we demonstrate that PTEN-L promotes type I interferon responses and antiviral innate immunity during viral infection in a phosphatase activity-dependent manner. Compared with canonical PTEN, PTEN-L also exerts its antiviral function when it is applied exogenously in protein form. This finding was confirmed in cell cultures and mouse infection models. Furthermore, PTEN-L enhances the responses of both type I interferon and proinflammatory cytokines, thus suggesting that PTEN-L might possess additional functions compared with those of PTEN. Thus, the antiviral function of PTEN-L may open an avenue for the use of PTEN-L in antiviral therapy, particularly in patients with PTEN-deficient tumors.

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PTEN secretion in exosomes

Cited by 21 publications

References 29 publications

PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer

PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer

The potential of tumor-derived exosomes for noninvasive cancer monitoring

PTEN-L promotes type I interferon responses and antiviral immunity

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