Contribution of classical end-joining to PTEN inactivation in p53-mediated glioblastoma formation and drug-resistant survival

Kang, Youn‐Jung; Balter, Barbara; Csizmadia, Eva; Haas, Brian R.; Sharma, Himanshu; Bronson, Roderick T.; Yan, Catherine T.

doi:10.1038/ncomms14013

Cited by 24 publications

(20 citation statements)

References 54 publications

(95 reference statements)

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“…Immunoblotting and subcellular fractionation were performed as previously described [ 12 ]. PFN1 (Abcam; ab118984, 1:2000), PTEN (Cell Signaling; 9188, 1:1000), Phospho-PTEN (Ser380/Thr382/383) (Cell Signaling; 9549, 1:1000), AKT (Cell Signaling; 4691, 1:1000), Phospho-Akt (Ser473) (Cell Signaling; 4060, 1:1000), α-Tubulin (Cell Signaling; 2144, 1:2000), SP1 (Santa cruz biotechnology; sc-59X, 1:2000), γH2AX (Abcam; ab11175, 1:2000), Chk1 (Santa cruz biotechnology, sc-377231, 1:1000), Phospho-Chk1 (Ser317) (Cell Signaling; 2344, 1:1000), Chk2 (Santa cruz biotechnology; sc-9064, 1:1000), Phospho-Chk2 (Thr68) (Novus Biologicals; NB100-92502, 1:1000), PARP (Cell Signaling; 9532, 1:1000), Cleaved-PARP(Asp214)(D64E10) (Cell Signaling; 5625, 1:1000) and β-actin (Abcam; ab54724, 1:2000), respectively followed by incubation with IgG-HRP (1:3000, Abcam, UK).…”

Section: Methodsmentioning

confidence: 99%

Profilin-1; a novel regulator of DNA damage response and repair machinery in keratinocytes

et al. 2021

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Profilin-1 (PFN1) regulates actin polymerization and cytoskeletal growth. Despite the essential roles of PFN1 in cell integration, its subcellular function in keratinocyte has not been elucidated yet. Here we characterize the specific regulation of PFN1 in DNA damage response and repair machinery. PFN1 depletion accelerated DNA damage-mediated apoptosis exhibiting PTEN loss of function instigated by increased phosphorylated inactivation followed by high levels of AKT activation. PFN1 changed its predominant cytoplasmic localization to the nucleus upon DNA damage and subsequently restored the cytoplasmic compartment during the recovery time. Even though γH2AX was recruited at the sites of DNA double strand breaks in response to DNA damage, PFN1-deficient cells failed to recruit DNA repair factors, whereas control cells exhibited significant increases of these genes. Additionally, PFN1 depletion resulted in disruption of PTEN-AKT cascade upon DNA damage and CHK1-mediated cell cycle arrest was not recovered even after the recovery time exhibiting γH2AX accumulation. This might suggest PFN1 roles in regulating DNA damage response and repair machinery to protect cells from DNA damage. Future studies addressing the crosstalk and regulation of PTEN-related DNA damage sensing and repair pathway choice by PFN1 may further aid to identify new mechanistic insights for various DNA repair disorders.

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Section: Methodsmentioning

confidence: 99%

Profilin-1; a novel regulator of DNA damage response and repair machinery in keratinocytes

et al. 2021

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“…IF staining using an antibody against α-SMA (1:500; Abcam, Cambridge, UK) was performed as previously described [20].…”

Section: Immunofluorescence and Microscopymentioning

confidence: 99%

Eupatilin treatment inhibits transforming growth factor beta-induced endometrial fibrosis in vitro

Lee

Hong

Yoon

et al. 2020

Clin Exp Reprod Med

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Objective: Endometrial fibrosis, the primary pathological feature of intrauterine adhesion, may lead to disruption of endometrial tissue structure, menstrual abnormalities, infertility, and recurrent pregnancy loss. At present, no ideal therapeutic strategy exists for this fibrotic disease. Eupatilin, a major pharmacologically active flavone from <i>Artemisia</i>, has been previously reported to act as a potent inducer of dedifferentiation of fibrotic tissue in the liver and lung. However, the effects of eupatilin on endometrial fibrosis have not yet been investigated. In this study, we present the first report on the impact of eupatilin treatment on transforming growth factor beta (TGF-β)-induced endometrial fibrosis.Methods: The efficacy of eupatilin on TGF-β–induced endometrial fibrosis was assessed by examining changes in morphology and the expression levels of fibrosis markers using immunofluorescence staining and quantitative real-time reverse-transcription polymerase chain reaction.Results: Eupatilin treatment significantly reduced the fibrotic activity of TGF-β–induced endometrial fibrosis in Ishikawa cells, which displayed more circular shapes and formed more colonies. Additionally, the effects of eupatilin on fibrotic markers including alpha-smooth muscle actin, hypoxia-inducible factor 1 alpha, collagen type I alpha 1 chain, and matrix metalloproteinase-2, were evaluated in TGF-β–induced endometrial fibrosis. The expression of these markers was highly upregulated by TGF-β pretreatment and recovered to the levels of control cells in response to eupatilin treatment.Conclusion: Our findings suggest that suppression of TGF-β–induced signaling by eupatilin might be an effective therapeutic strategy for the treatment of endometrial fibrosis.

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“…Histology and immunohistochemistry were performed as described [35] by using antibodies to Integrin β3 (Cell Signaling; #13166; 1:100), and OPN (Enzo; ADI-905-629; 1:100) and detected with HRP-conjugated anti-mouse or rabbit secondary antibodies, and counterstained with DAPI (Sigma).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Immuno uorescence staining was performed as previous described [35]. Localization studies were performed using antibody to CXCR4 (Invitrogen; PA3-305, 1:100), CXCR7 (Novus; NBP2-58162, 1:100), integrin αvβ3 (MILLIPORE; MAB1976, 1:100), HIF1α (Cell signaling technology; #3434, 1:50), CD31 (abcam; ab28364, 1:100), and CD34 (abcam; ab8563, 1:100), and further incubated with anti-rabbit IgG uorescence (Invitrogen) or anti-mouse IgG uorescence (Invitrogen).…”

Section: Immuno Uorescence and Microscopymentioning

confidence: 99%

Embryo-Derived Chemokine CXCL12 Enhances Pregnancy Outcome via Improvement of Endometrial Receptivity

Koo

Yoon

Hong

et al. 2020

Preprint

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Background: Successful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although a remarkable improvement of assisted reproductive technology (ART) has been achieved over the last few decades, there are still a number of infertile women experiencing frequent ART failure after repeated attempts due to many unsolved problems including repeated failure of implantation. Many substances have been suggested to improve the rates of embryo implantation by enhancing the endometrial receptivity for the patients who are suffering from repeated failure of implantation. However, despite these numerous extensive research work, there are currently no effective evidence-based treatments to prevent or cure this condition. Therefore, here we aim to suggest non-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention to solve this problem.Results: We demonstrated that chemokine CXCL12 is derived from pre- and peri-implanting embryos and its interaction with endometrial CXCR4 and CXCR7 enhances endometrial receptivity and significantly promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in vivo, which is a completely non-invasive treatment strategy, improved endometrial receptivity showing increased integrin b3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Conclusions: Our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a non-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.

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Contribution of classical end-joining to PTEN inactivation in p53-mediated glioblastoma formation and drug-resistant survival

Cited by 24 publications

References 54 publications

Profilin-1; a novel regulator of DNA damage response and repair machinery in keratinocytes

Profilin-1; a novel regulator of DNA damage response and repair machinery in keratinocytes

Eupatilin treatment inhibits transforming growth factor beta-induced endometrial fibrosis in vitro

Embryo-Derived Chemokine CXCL12 Enhances Pregnancy Outcome via Improvement of Endometrial Receptivity

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