Nuclear architecture and the structural basis of mitotic memory

Soujanya, Mamilla; Bihani, Ashish; Hajirnis, Nikhil; Pathak, Rashmi U.; Mishra, Rakesh

doi:10.1007/s10577-023-09714-y

Cited by 4 publications

(1 citation statement)

References 221 publications

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“…Serial reimplantation was not only a model of recurrence and metastasis, but we also wanted to observe the stability of the transfected Oct3/4 gene in these cells. Unlike some transcription factors, such as GATA1-4, BMI1and HMG1, the endogenous Oct3/4 usually does not show "mitotic bookmarking", thus is not carried over after replication by default [29,30]. Clonal selection is a possibility and could have been aided by the overactivation of Oct3/4 gene as well as the related ONSS transcriptome that rendered the predisposition to metastasis and increased tumor initiation potential.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability

Rajan

Krutilina

Игнатова

et al. 2023

IJMS

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Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the Oct3/4 network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay. The tumor-seeding potential in immunocompromised (NOD-SCID) mice and DEGs in the tumors were also assessed along with the intra-tumor (CD44+/CD24-) expression using flow cytometry. Unlike 2-D cultures, the Oct3/4-GFP expression was homogenous and stable in 3-D mammospheres developed from BCSCs. A total of 25 DEGs including Gata6, FoxA2, Sall4, Zic2, H2afJ, Stc1 and Bmi1 were identified in Oct3/4 activated cells coupled with a significantly increased resistance to paclitaxel. In mice, the higher Oct3/4 expression in tumors correlated with enhanced tumorigenic potential and aggressive growth, with metastatic lesions showing a >5-fold upregulation of DEGs compared to orthotopic tumors and variability in different tissues with the highest modulation in the brain. Serially re-implanting tumors in mice as a model of recurrence and metastasis highlighted the sustained upregulation of Sall4, c-Myc, Mmp1, Mmp9 and Dkk1 genes in metastatic lesions with a 2-fold higher expression of stem cell markers (CD44+/CD24-). Thus, Oct3/4 transcriptome may drive the differentiation and maintenance of BCSCs, promoting their tumorigenic potential, metastasis and resistance to drugs such as paclitaxel with tissue-specific heterogeneity.

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Section: Discussionmentioning

confidence: 99%

Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability

Rajan

Krutilina

Игнатова

et al. 2023

IJMS

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Epigenotoxicity: Decoding the epigenetic imprints of genotoxic agents and their implications for regulatory genetic toxicology

Godschalk,

Faulk,

LaRocca

et al. 2024

Environ and Mol Mutagen

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Regulatory genetic toxicology focuses on DNA damage and subsequent gene mutations. However, genotoxic agents can also affect epigenetic marks, and incorporation of epigenetic data into the regulatory framework may thus enhance the accuracy of risk assessment. Additionally, epigenetic alterations may identify non‐genotoxic carcinogens that are not captured with the current battery of tests. Epigenetic alterations could also explain long‐term consequences and potential transgenerational effects in the absence of DNA mutations. Therefore, at the 2022 International Workshops on Genotoxicity Testing (IWGT) in Ottawa (Ontario, Canada), an expert workgroup explored whether including epigenetic endpoints would improve regulatory genetic toxicology. Here we summarize the presentations and the discussions on technical advancements in assessing epigenetics, how the assessment of epigenetics can enhance strategies for detecting genotoxic and non‐genotoxic carcinogens and the correlation between epigenetic alterations with other relevant apical endpoints.

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Epigenetic Inheritance

Fallet

2024

Epigenetics in Biological Communication

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Nuclear architecture and the structural basis of mitotic memory

Cited by 4 publications

References 221 publications

Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability

Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability

Epigenotoxicity: Decoding the epigenetic imprints of genotoxic agents and their implications for regulatory genetic toxicology

Epigenetic Inheritance

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