ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways

Selmi, Tommaso; Martello, Andrea; Vignudelli, Tatiana; Ferrari, Érika; Grande, Alexis; Gemelli, Claudia; Salomoni, Paolo; Ferrari, Sérgio; Zanocco-Marani, Tommaso

doi:10.4161/cc.20309

Cited by 27 publications

(26 citation statements)

References 43 publications

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“…4D) of U87MG cells. Consistent with these findings, expression of TTP has been shown to suppress cell growth and invasion in brain and colon cancer cells (Selmi et al, 2012;Stoecklin et al, 2003). These findings indicate that TTP performs a tumor suppressor function by regulating the mRNA stability of ARE-containing genes such as uPA and uPAR.…”

Section: Discussionsupporting

confidence: 72%

Tristetraprolin Inhibits the Growth of Human Glioma Cells through Downregulation of Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor mRNAs

Ryu

Yoon

Lee

et al. 2015

Molecules and Cells

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Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Downregulatoion of the uPA and uPAR has been reported to inhibit the growth glioblastoma. Here, we demonstrate that tristetraprolin (TTP) inhibits the growth of U87MG human glioma cells through downregulation of uPA and uPAR. Our results show that expression level of TTP is inversely correlated with those of uPA and uPAR in human glioma cells and tissues. TTP binds to the AU-rich elements within the 3' untranslated regions of uPA and uPAR and overexpression of TTP decreased the expression of uPA and uPAR through enhancing the degradation of their mRNAs. In addition, overexpression of TTP inhibited the growth and invasion of U87MG cells. Our findings implicate that TTP can be used as a promising therapeutic target to treat human glioma.

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Section: Discussionsupporting

confidence: 72%

Tristetraprolin Inhibits the Growth of Human Glioma Cells through Downregulation of Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor mRNAs

Ryu

Yoon

Lee

et al. 2015

Molecules and Cells

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“…Previous studies reported that TTP regulated the mRNA decay of PIM1 and PIM3 but not that of PIM2 (Kim et al ., ; Mahat et al ., ; Selmi et al ., ). Our study showed a negative feedback loop between PIM family proteins and TTP through the PIM2‐degradation of TTP.…”

Section: Discussionmentioning

confidence: 97%

PIM2 interacts with tristetraprolin and promotes breast cancer tumorigenesis

et al. 2018

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Tristetraprolin (TTP) is an AU‐rich element‐binding protein that regulates mRNA stability and plays important roles in cancer. The mechanisms by which TTP is regulated in breast cancer are poorly understood. Using multiple biochemical approaches, we found that proviral insertion in murine lymphomas 2 (PIM2) is a novel binding partner of TTP. Interestingly, PIM2 decreased TTP protein levels independent of its kinase activity. PIM2 instead targeted TTP protein for degradation via the ubiquitin‐proteasome pathway. Furthermore, immunohistochemical staining showed that PIM2 and TTP protein levels were negatively correlated in human breast cancer samples. Indeed, PIM2 overexpression de‐repressed TTP‐mediated inhibition of breast cancer cell proliferation and migration in vitro and promoted breast tumor xenograft growth in vivo. These findings demonstrate an important role for the PIM2‐TTP complex in breast cancer tumorigenesis, suggesting that PIM2 may represent a potential therapeutic target for breast cancer treatment.

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“…Even though the immunophenotype is similar for LSC derived from different cells of origin, there are reproducible differences in gene expression. For example, Evi1, c-jun, Fos1, Bcl6 (Parekh et al, 2008), Gsr1, Nedd9 and Zfp36 (Selmi et al, 2012) are highly expressed in HSC-derived LSC but not GMP derived LSC (Supplemental Figure 6F). Therefore we demonstrate that the cell in which the oncogene is initially expressed can influence the final gene expression program of the LSC even if the LSC represents a stage of hematopoietic development further downstream of the HSC.…”

Section: Discussionmentioning

confidence: 99%

Cell of origin determines clinically relevant subtypes of MLL-rearranged AML

et al. 2012

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Summary MLL-fusion proteins can induce acute myeloid leukemias (AML) from either hematopoietic stem cells (HSC) or granulocyte macrophage progenitors (GMP), but it remains unclear if the cell of origin influences the biology of the resultant leukemia. MLL-AF9 transduced single HSC or GMP could be continuously replated, but HSC-derived clones were more likely than GMP-derived clones to initiate AML in mice. Leukemia stem cells derived from either HSC or GMP had a similar immunophenotype consistent with a maturing myeloid cell (LGMP). Gene expression analyses demonstrated that LGMP inherited gene expression programs from the cell of origin including high-level Evi-1 expression in HSC derived LGMP. The gene expression signature of LGMP derived from HSC was enriched in poor prognosis human MLL-rearranged AML in three independent data sets. Moreover, global 5’-mC levels were elevated in HSC-derived leukemias as compared to GMP-derived leukemias. This mirrored a difference seen in 5-mC between MLL-rearranged human leukemias that are either EVI1-positive or EVI1-negative. Finally, HSC derived leukemias were more resistant to chemotherapy than GMP-derived leukemias. These data demonstrate that the cell of origin influences the gene expression profile, the epigenetic state, and the drug response in AML, and that these differences can account for clinical heterogeneity within a molecularly defined group of leukemias. Significance Human AMLs are heterogeneous even within subtype defined by a specific genetic lesion such as MLL-translocations and this leads to variable clinical outcomes. The developmental stage (or epigenetic state) of the cell in which leukemogenic transformation is initiated may contribute to the ultimate disease phenotype. We used a well established model of MLL-AF9 mediated AML and transformation of single cells to test the relevance of the leukemia cell of origin on AML development, gene expression profiles, DNA methylation and chemotherapy response. We show that HSC derived AML models human high-risk/poor outcome AML pool, and that we can recapitulate important clinical subtypes of human MLL-rearranged AML through the transformation of different cell types. These data demonstrate that the cell of origin can influence the phenotype of a resultant leukemia even if the initiating genetic lesion is the same.

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ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways

Abstract: (2012) ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways, Cell

Cited by 27 publications

References 43 publications

Tristetraprolin Inhibits the Growth of Human Glioma Cells through Downregulation of Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor mRNAs

Tristetraprolin Inhibits the Growth of Human Glioma Cells through Downregulation of Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor mRNAs

PIM2 interacts with tristetraprolin and promotes breast cancer tumorigenesis

Cell of origin determines clinically relevant subtypes of MLL-rearranged AML

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