Antineoplastic Nature of WWOX in Glioblastoma Is Mainly a Consequence of Reduced Cell Viability and Invasion

Kałuzińska, Żaneta; Kośla, Katarzyna; Kołat, Damian; Płuciennik, Elżbieta

doi:10.3390/biology12030465

Cited by 3 publications

(9 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The initial step of the current analysis was intended to identify a common expression profile for U87MG, T98G, and U251MG cell lines owing to their coherence in results from the previous study following WWOX overexpression ( Kaluzinska-Kolat et al, 2023 ). DBTRG-05MG was temporarily excluded from establishing consensus module-trait relationships since it caused technical issues preventing analysis.…”

Section: Resultsmentioning

confidence: 99%

“…A more detailed summary of gene ontology is collected in Supplementary Table 5 . Some annotated processes can be certified using data from our previous research ( Kaluzinska-Kolat et al, 2023 ). ORA of the entire network and the parts consistent for all cell lines has repeatedly indicated cell death and apoptotic signaling pathway regulation.…”

Section: Resultsmentioning

confidence: 99%

“…The cell culture, procedure of lentiviral transduction for WWOX upregulation, and its confirmation are described in our preceding study ( Kaluzinska-Kolat et al, 2023 ). Briefly, four cell lines representing glioblastoma (U87MG, T98G, U251MG, DBTRG-05MG) were purchased from the European collection of cell cultures (ECACC), incubated at 37°C in a humidified atmosphere of 5% CO 2 , and cultured in MEM (T98G), EMEM (U87MG and U251MG) or RPMI-1640 (DBTRG-05MG) medium supplemented with L-glutamine, fetal bovine serum, and Antibiotic-Antimycotic.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we investigated the phenotypic heterogeneity of four GBM cell lines (U87MG, T98G, U251MG, and DBTRG-05MG) and revealed some discrepancies in the results from in vitro assays following the ectopic overexpression of WW domain-containing oxidoreductase ( WWOX ) ( Kaluzinska-Kolat et al, 2023 ; Varricchio et al, 2023 ). The literature on the role of this gene in brain development and pathology is generally of a reasonable extent and emphasizes its importance in nervous tissue ( Kosla et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that WWOX mitigates the glioblastoma’s infiltrative potential, and its loss can promote the migration of cancer cells ( Chiang et al, 2012 , 2013 ). Our previous research concluded that the anti-GBM activity of WWOX is mainly a consequence of reduced cell viability and invasion ( Kaluzinska-Kolat et al, 2023 ). However, while most of the data indicated the antineoplastic activity of WWOX , discrepancies related to colony growth and formation were noticed in one of the above GBM cell lines, i.e., DBTRG-05MG.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Kałuzińska-Kołat,

Kołat,

Kośla

et al. 2023

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

IntroductionGlioblastoma (GBM) is notorious for its clinical and molecular heterogeneity, contributing to therapeutic failure and a grim prognosis. WWOX is one of the tumor suppressor genes important in nervous tissue or related pathologies, which was scarcely investigated in GBM for reliable associations with prognosis or disease progression despite known alterations. Recently, we observed a phenotypic heterogeneity between GBM cell lines (U87MG, T98G, U251MG, DBTRG-05MG), among which the anti-GBM activity of WWOX was generally corresponding, but colony growth and formation were inconsistent in DBTRG-05MG. This prompted us to investigate the molecular landscapes of these cell lines, intending to translate them into the clinical context.MethodsU87MG/T98G/U251MG/DBTRG-05MG were subjected to high-throughput sequencing, and obtained data were explored via weighted gene co-expression network analysis, differential expression analysis, functional annotation, and network building. Following the identification of the most relevant DBTRG-distinguishing driver genes, data from GBM patients were employed for, e.g., differential expression analysis, survival analysis, and principal component analysis.ResultsAlthough most driver genes were unique for each cell line, some were inversely regulated in DBTRG-05MG. Alongside driver genes, the differentially-expressed genes were used to build a WWOX-related network depicting protein–protein interactions in U87MG/T98G/U251MG/DBTRG-05MG. This network revealed processes distinctly regulated in DBTRG-05MG, e.g., microglia proliferation or neurofibrillary tangle assembly. POLE4 and HSF2BP were selected as DBTRG-discriminating driver genes based on the gene significance, module membership, and fold-change. Alongside WWOX, POLE4 and HSF2BP expression was used to stratify patients into cell lines-resembling groups that differed in, e.g., prognosis and treatment response. Some differences from a WWOX-related network were certified in patients, revealing genes that clarify clinical outcomes. Presumably, WWOX overexpression in DBTRG-05MG resulted in expression profile change resembling that of patients with inferior prognosis and drug response. Among these patients, WWOX may be inaccessible for its partners and does not manifest its anti-cancer activity, which was proposed in the literature but not regarding glioblastoma or concerning POLE4 and HSF2BP.ConclusionCell lines data enabled the identification of patients among which, despite high expression of WWOX tumor suppressor, no advantageous outcomes were noted due to the cancer-promoting profile ensured by other genes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Kałuzińska-Kołat,

Kołat,

Kośla

et al. 2023

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

Lin,

Liu,

et al. 2024

J Hematol Oncol

View full text Add to dashboard Cite

Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and integration of medicine and engineering technology therapy, the efficacy of these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny of the inhibitory and immunosuppressive milieu within GBM has underscored the significance of cellular constituents of the GBM microenvironment and their interactions with malignant cells and neurons. Novel immune and targeted therapy strategies have emerged, offering promising avenues for advancing GBM treatment. One pivotal mechanism orchestrating immunosuppression in GBM involves the aggregation of myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAM), and regulatory T cells (Tregs). Among these, MDSCs, though constituting a minority (4–8%) of CD45+ cells in GBM, play a central component in fostering immune evasion and propelling tumor progression, angiogenesis, invasion, and metastasis. MDSCs deploy intricate immunosuppressive mechanisms that adapt to the dynamic tumor microenvironment (TME). Understanding the interplay between GBM and MDSCs provides a compelling basis for therapeutic interventions. This review seeks to elucidate the immune regulatory mechanisms inherent in the GBM microenvironment, explore existing therapeutic targets, and consolidate recent insights into MDSC induction and their contribution to GBM immunosuppression. Additionally, the review comprehensively surveys ongoing clinical trials and potential treatment strategies, envisioning a future where targeting MDSCs could reshape the immune landscape of GBM. Through the synergistic integration of immunotherapy with other therapeutic modalities, this approach can establish a multidisciplinary, multi-target paradigm, ultimately improving the prognosis and quality of life in patients with GBM.

show abstract

CheekAge, a next-generation epigenetic buccal clock, is predictive of mortality in human blood

Shokhirev,

Kramer,

Corley

et al. 2024

Front. Aging

View full text Add to dashboard Cite

While earlier first-generation epigenetic aging clocks were trained to estimate chronological age as accurately as possible, more recent next-generation clocks incorporate DNA methylation information more pertinent to health, lifestyle, and/or outcomes. Recently, we produced a non-invasive next-generation epigenetic clock trained using Infinium MethylationEPIC data from more than 8,000 diverse adult buccal samples. While this clock correlated with various health, lifestyle, and disease factors, we did not assess its ability to capture mortality. To address this gap, we applied CheekAge to the longitudinal Lothian Birth Cohorts of 1921 and 1936. Despite missing nearly half of its CpG inputs, CheekAge was significantly associated with mortality in this longitudinal blood dataset. Specifically, a change in one standard deviation corresponded to a hazard ratio (HR) of 1.21 (FDR q = 1.66e-6). CheekAge performed better than all first-generation clocks tested and displayed a comparable HR to the next-generation, blood-trained DNAm PhenoAge clock (HR = 1.23, q = 2.45e-9). To better understand the relative importance of each CheekAge input in blood, we iteratively removed each clock CpG and re-calculated the overall mortality association. The most significant effect came from omitting the CpG cg14386193, which is annotated to the gene ALPK2. Excluding this DNA methylation site increased the FDR value by nearly threefold (to 4.92e-06). We additionally performed enrichment analyses of the top annotated CpGs that impact mortality to better understand their associated biology. Taken together, we provide important validation for CheekAge and highlight novel CpGs that underlie a newly identified mortality association.

show abstract

Antineoplastic Nature of WWOX in Glioblastoma Is Mainly a Consequence of Reduced Cell Viability and Invasion

Cited by 3 publications

References 115 publications

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

CheekAge, a next-generation epigenetic buccal clock, is predictive of mortality in human blood

Contact Info

Product

Resources

About