PARK7 maintains the stemness of glioblastoma stem cells by stabilizing epidermal growth factor receptor variant III

Kim, Jeong‐Yub; Kim, Hee‐Jin; Jung, Chan-Woong; Choi, Byung-Il; Lee, Dae-Hee; Park, Myungjin

doi:10.1038/s41388-020-01543-1

Cited by 26 publications

(25 citation statements)

References 58 publications

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“…Interactions between all identified stem cell markers are preponderant in establishing a stem cell phenotype, and it is therefore difficult to consider any one of them independently of the others. For example, when PARK7—involved in the maintenance of the GBM stem cell strain—is knocked down, the expression of nestin decreases, along with that of EGFRvIII, SOX2, OCT4, NANOG, NOTCH1, non-phospho-β-catenin, Musashi1, and BMI-1, as well as the ability to form spheres [ 23 ]. It is known that Notch-1 promotes nestin expression in glioma cells and inhibits their differentiation, so the involvement of Notch-1 in R2J-GS cell activity would also be of interest to better understand the workings underlying the expression of these markers.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of Sodium Selenite in Mice: Toxicological and Tumor Regression Studies after Striatum Implantation of Human Glioblastoma Stem Cells

Larrouquère

Berthier²,

Chovelon

et al. 2021

IJMS

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Glioblastoma (GBM) is the most aggressive malignant glioma, with a very poor prognosis; as such, efforts to explore new treatments and GBM’s etiology are a priority. We previously described human GBM cells (R2J-GS) as exhibiting the properties of cancer stem cells (growing in serum-free medium and proliferating into nude mice when orthotopically grafted). Sodium selenite (SS)—an in vitro attractive agent for cancer therapy against GBM—was evaluated in R2J-GS cells. To go further, we launched a preclinical study: SS was given orally, in an escalation-dose study (2.25 to 10.125 mg/kg/day, 5 days on, 2 days off, and 5 days on), to evaluate (1) the absorption of selenium in plasma and organs (brain, kidney, liver, and lung) and (2) the SS toxicity. A 6.75 mg/kg SS dose was chosen to perform a tumor regression assay, followed by MRI, in R2J-GS cells orthotopically implanted in nude mice, as this dose was nontoxic and increased brain selenium concentration. A group receiving TMZ (5 mg/kg) was led in parallel. Although not reaching statistical significance, the group of mice treated with SS showed a slower tumor growth vs. the control group (p = 0.08). No difference was observed between the TMZ and control groups. We provide new insights of the mechanisms of SS and its possible use in chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of Sodium Selenite in Mice: Toxicological and Tumor Regression Studies after Striatum Implantation of Human Glioblastoma Stem Cells

Larrouquère

Berthier²,

Chovelon

et al. 2021

IJMS

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“…Since DJ-1 has been associated with the bladder, prostate, colorectal and gastric cancers etc. [32,33], it is anticipated that SG2NA and some of its associated proteins would also be involved in cancer. Such notion is further strengthened by our recent observation that overexpression of 35 kDa SG2NA and knocking down the 78 kDa in NIH3T3 cells induces certain markers of epithelial to mesenchymal transition [21].…”

Section: Discussionmentioning

confidence: 99%

The Profile of Expression of SG2NAs Differs Between Cancer Types and it is Involved in the Reprogramming of Tumour Cell Proteome.

Bisoyi

Devi

Besra

et al. 2021

Preprint

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Striatin and SG2NA are scaffold proteins that from signalling complexes called STRIPAK. It has been associated with cancer and other diseases. Our earlier studies have shown that SG2NA forms a complex with the cancer associate protein DJ-1 and signalling kinase Akt, promoting cancer cell survival. In the present study, we used bioinformatics analyses to confirm the existence of two isoforms of human SG2NA i.e., 78 and 87 kDas. In addition, several smaller isoforms like 35 kDa were also seen in western blot analyses of human cell lysates. The expression of these isoforms varies between different human cancer cell lines. Also, the protein level does not corroborate with its transcript level, suggesting a complex regulation of its expression. In breast tumour tissues, the expression of the 35 and 78 kDa isoforms was higher as compared to the adjacent normal tissues, while the 87 kDa isoform was detected in the breast tumour tissues only. With the progression of stages of breast cancer, the expression of 78 kDa isoform decreased, while 87 kDa became undetectable. In coimmunoprecipitation assay, the profile of SG2NA interactome in breast tumor vis-à-vis adjacent normal breast tissues shows hundreds of common proteins, while some proteins specifically interacted in breast tumour tissue only. We conclude that SG2NA is involve in diverse cellular pathways and have roles in cellular reprogramming during tumorigenesis.

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“…Conversely, the overexpression of PARK7 in non-GIC CD133 (-) increased self-renewal activities, migration, and IR resistance. Most important of all, PARK7 knockdown increased mouse survival and IR sensitivity in vivo [31].…”

Section: Advances In Rtmentioning

confidence: 97%

“…PARK7 is a ubiquitous human protein involved in many cellular processes including cell proliferation, transcriptional regulation, cell differentiation, protection from oxidative stress, and maintenance of mitochondrial function. Its possible effects on the stemness and radioresistance of GICs has been studied by Kim et al [31]. PARK7 was found to be expressed more in GICs than in differentiated cells.…”

Section: Advances In Rtmentioning

confidence: 98%

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

Fròsina

2021

IJMS

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Albeit the effort to develop targeted therapies for patients with high-grade gliomas (WHO grades III and IV) is evidenced by hundreds of current clinical trials, radiation remains one of the few effective therapeutic options for them. This review article analyzes the updates on the topic “radiotherapy of high-grade gliomas” during the period 1 January 2021–30 June 2021. The high number of articles retrieved in PubMed using the search terms (“gliom* and radio*”) and manually selected for relevance indicates the feverish research currently ongoing on the subject. During the last semester, significant advances were provided in both the preclinical and clinical settings concerning the diagnosis and prognosis of high-grade gliomas, their radioresistance, and the inevitable side effects of their treatment with radiation. The novel information concerning tumor radiosensitization was of special interest in terms of therapeutic perspective and was discussed in detail.

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PARK7 maintains the stemness of glioblastoma stem cells by stabilizing epidermal growth factor receptor variant III

Cited by 26 publications

References 58 publications

Preclinical Evaluation of Sodium Selenite in Mice: Toxicological and Tumor Regression Studies after Striatum Implantation of Human Glioblastoma Stem Cells

Preclinical Evaluation of Sodium Selenite in Mice: Toxicological and Tumor Regression Studies after Striatum Implantation of Human Glioblastoma Stem Cells

The Profile of Expression of SG2NAs Differs Between Cancer Types and it is Involved in the Reprogramming of Tumour Cell Proteome.

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

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