Jekaterina Erenpreisa

Latvian Biomedical Research and Study Centre | LBMC

Metastatic cancer is rarely cured by current DNA damaging treatments, apparently due to the development of resistance. However, recent data indicates that tumour cells can elicit the opposing processes of senescence and stemness in response to these treatments, the biological significance and molecular regulation of which is currently poorly unders...

Liver hepatocytes possess remarkable regenerative capabilities, yet severe damage may compromise this process. Liver progenitor (“oval”) cells exhibit the potential to differentiate into both hepatocytes and cholangiocytes, making them promising candidates for cell therapy. However, their mechanisms in liver regeneration are not clear. Here, on rat...

The early stress response by AP-1 (FOS/JUN), supported by upregulation of c-Myc and involved in cell-fate changes and adaptation to hostile environments, is increased in cancer. The review shows the biphasic character of this response with negative feed-back typically lasting a few hours as a feature of the genome regulation by self-organising crit...

Telomeres in epithelial tumours are usually maintained by telomerase, however, in the breast cancer MDA-MB-231 cell line, polyploid cells, induced by doxorubicin (DOX) were found, after mitotic slippage, transiently shifting to recombinatory alternative telomere lengthening (ALT) in PML bodies (APBs). The involvement of the meiotic recombination pr...

Telomeres in epithelial tumours are usually maintained by telomerase, however, in the breast cancer MDA-MB-231 cell line, polyploid cells, induced by doxorubicin (DOX) were found, after mitotic slippage, transiently shifting to recombinatory alternative telomere lengthening (ALT) in PML bodies (APBs). The involvement of the meiotic recombination pr...

Cancer is globally increasing [...]

The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy...

The increasing frequency of male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis-antigens (CTA). The phylostratigraphy analysis of the human gen...

In our recent work, we observed that triple-negative breast cancer MDA-MB-231 cells respond to doxorubicin (DOX) via “mitotic slippage” (MS), discarding cytosolic damaged DNA during the process that provides their resistance to this genotoxic treatment. We also noted two populations of polyploid giant cells: those budding surviving offspring, versu...

Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing genetic interactions between different...

Abstract: The expression of gametogenesis-related (GG) genes and proteins, as well as whole genome duplications (WGD), are the hallmarks of cancer related to poor prognosis. Currently, it is not clear if these hallmarks are random processes associated only with genome instability or are programmatically linked. Our goal was to elucidate this via a...

The purpose of our studies is to elucidate the nature of massive control of the whole genome expression with a particular emphasis on cell-fate change. The whole genome expression is coordinated by the emergence of a critical point (CP: a peculiar set of biphasic genes) with the genome acting as an integrated dynamical system. In response to stimul...

The convergence between a statistical mechanics and biological approach in elucidating some basic features of cell differentiation opens new avenues of research in gene expression regulation and holds some promises in terms of a re-differentiation approach to a cancer cure. The message emerging from two recent papers by the authors of the present c...

Here, we review the role of the circadian clock (CC) in the resistance of cancer cells to genotoxic treatments in relation to whole-genome duplication (WGD) and telomere-length regulation. The CC drives the normal cell cycle, tissue differentiation, and reciprocally regulates telomere elongation. However, it is deregulated in embryonic stem cells (...

The Circadian Clock (CC) drives the normal cell cycle and reciprocally regulates telomere elongation. However, it can be deregulated in cancer, embryonic stem cells (ESC) and the early embryo. Here, its role in the resistance of cancer cells to genotoxic treatments was assessed in relation to whole-genome duplication (WGD) and telomere regulation....

The purpose of our studies is to elucidate the nature of massive control of whole genome expression with a particular emphasis on cell-fate change. Whole genome expression is coordinated by the emergence of a critical point (CP: a peculiar set of bi-phasic genes) through the genome-engine. In response to stimuli, the genome expression self-organize...

Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear information of the genetic code is re...

Finding out how cells prepare for fate change during differentiation commitment was our task. To address if the constitutive pericentromere associated domains (PADs) may be involved, we used a model system with known transcriptome data, MCF-7 breast cancer cells treated with the ErbB3 ligand heregulin (HRG), which induces differentiation and is use...

The fundamental understanding of how Cancer initiates, persists and then progresses is evolving. High-resolution technologies, including single-cell mutation and gene expression measurements, are now attainable, providing an ever-increasing insight into the molecular details. However, this higher resolution has shown that somatic mutation theory it...

Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtai...

The ectopic expression of cancer testis (CT) antigens and classic meiotic genes is characteristic and a hallmark of poor prognosis of melanoma disease. Here the potential mechanisms of meiotic influence on the cell and life cycle of malignant melanoma are reviewed in the genetic, epigenetic, and evolutionary aspects. The involved mutant B-RAF and N...

Finding out how cells with the same genome change fates in differentiation commitment is a challenge of biology. We used MCF-7 breast cancer cells treated with the ErbB2 ligand heregulin (HRG), which induces differentiation, to address if and how the constitutive pericentromere-associated domains (PADs) may be involved in this process. PAD-specific...

Mitotic slippage (MS), the incomplete mitosis that results in a doubled genome in interphase, is a typical response of TP53-mutant tumors resistant to genotoxic therapy. These polyploidized cells display premature senescence and sort the damaged DNA into the cytoplasm. In this study, we explored MS in the MDA-MB-231 cell line treated with doxorubic...

The apparent lack of success in curing cancer that was evidenced in the last four decades of molecular medicine indicates the need for a global re-thinking both its nature and the biological approaches that we are taking in its solution. The reductionist, one gene/one protein method that has served us well until now, and that still dominates in bio...

Objective: Rat liver stem-like epithelial cells (WB-F344) that under certain conditions may differentiate into hepatocyte and biliary lineages were subjected to acute X-irradiation with the aim to examine cell cycle peculiarities during the course of survival. Materials and methods: Suspensions of WB-F344 cells that grew as a monolayer and reach...

Jānis Olģerts Ērenpreiss (1929–1996) was a prominent Latvian cancer researcher and theoretician. Starting out as a student, he contributed to the embryonal theory of cancer, experimentally proving the differentiation and regenerative normalisation capabilities of tumour cells. His theoretical work, presented in its most complete form in his final m...

Triple negative MDA-MB-231 (mt TP53) breast cancer cells after doxorubicin treatment underwent cellular senescence, but they were still capable of recovering the clonogenic growth. On day 4 after treatment most of the cells expressed hallmarks of senescence, such as: arrest in the G2/M phase of the cell cycle, increased level of the cell cycle inhi...

Triploidy in cancer is associated with poor prognosis, but its origins remain unclear. Here, we attempted to differentiate between random chromosomal and whole-genome origins of cancer triploidy. In silico meta-analysis was performed on 15 male malignant and five benign tumor cohorts (2928 karyotypes) extracted from the Mitelman Database, comparing...

Near-triploid human tumors are frequently resistant to radio/chemotherapy through mechanisms that are unclear. We recently reported a tight association of male tumor triploidy with XXY karyotypes based on a meta-analysis of 15 tumor cohorts extracted from the Mitelman database. Here we provide a conceptual framework of the digyny-like origin of thi...

Triploidy in cancer is associated with poor prognosis but its origins remain unclear. Here, we attempted to differentiate between random chromosomal and whole-genome origins of cancer triploidy. In silico meta-analysis was performed on 15 male malignant and 5 benign tumour cohorts (2928 karyotypes) extracted from the Mitelman Database, comparing th...

Background. Discrepancies in the interpretation of breast cancer therapeutic responses still exist mainly because of lack of standardized assessment criteria and methods. Objective. DNA content profiling of cells in the affected (cancerous) tissue before and after neoadjuvant chemotherapy (NAC) was applied to facilitate interpretation of therapeu...

The nuclear envelope-associated epichromatin and its sheets are composed of DNA A-form packed as nucleosomal superbeads which construct vehicles for the gear-wheel nuclear traffic Jekaterina Erenpreisa1*, Kristine Salmina1, Jekabs Krigerts1, Turs Selga2, Talivaldis Freivalds2 1Latvian Biomedical Research & Study Center, Ratsupites 1, Riga, LV1067...

Polyploidy reprograms regulatory pathways towards unicellular mode: the role in stress response, drug resistance, growth and cancer Anatskaya OV*, Erenpreisa J**, Giuliani A***, Salmina K**, Vinogradov AE*. *Institute of Cytology, Saint Petersburg, Russia ** Latvian Biomedical Research and Study Centre, Riga, Latvia *** Istituto Superiore di Sani...

Triploidy in cancer is associated with poor prognosis but its origins remain unclear. Here, based on frequent X-chromosome doubling in male tumours we attempted to differentiate between a random chromosomal origin and whole-genome origin of cancer triploidy. In silico meta-analysis was performed on 15 male malignant and 5 benign tumour cohorts (292...

Aneuploidy should compromise cellular proliferation but paradoxically favours tumour progression and poor prognosis. Here, we consider this paradox in terms of our most recent observations of chemo/radio-resistant cells undergoing reversible polyploidy. The latter perform the segregation of two parental groups of end-to-end linked dyads by pseudo-m...

Aneuploidy should compromise cellular proliferation but paradoxically favours tumour progression and poor prognosis. Here, we consider this paradox in terms of our most recent observations of chemo/radio-resistant cells undergoing reversible polyploidy. The latter perform segregation of two parental groups of end-to-end linked dyads by pseudo-mitos...

Abstract in MOJ immunology Background: Polyploid cells exist in all mammalian tissues where they were searched. In physiological conditions polyploidy is a part of development and differentiation programs. In stressful condition it may promote pathological processes, including carcinogenesis. Aim and Methods: Currently, the impact of polyploidy on...

The chromatin observed by conventional electron microscopy under the nuclear envelope constitutes a single layer of dense 30–35 nm granules, while ∼30 nm fibrils laterally attached to them, form large patches of lamin-associated domains (LADs). This particular surface “epichromatin” can be discerned by specific (H2A+H2B+DNA) conformational antibody...

The epigenetic mechanisms underlying chemoresistance in cancer cells resulting from drug-induced reversible senescence are poorly understood. Chemoresistant ESC-like embryonal carcinoma PA1 cells treated with etoposide (ETO) were previously found to undergo prolonged G2 arrest with transient p53-dependent upregulation of opposing fate regulators, p...

Theories of cancer are central to our understanding of biology and receive frequent refinement. Here, we propose a link between key aspects of the atavistic theory of cancer and the capacity of polyploidy to access transcriptional networks of unicellular organisms. Polyploid cells are known to display greater capacity for adaptation to environmenta...

Theories of cancer are central to our understanding of biology and receive frequent refinement. Here, we propose a link between key aspects of the atavistic theory of cancer and the capacity of polyploidy to access transcriptional networks of unicellular organisms. Polyploid cells are known to display greater capacity for adaptation to environmenta...

Etoposide-treated embryonal carcinoma PA1 cells (wt TP53) and Doxorubicine-treated breast cancer MDA-MB-231 (mt TP53) underwent accelerated cell senescence, but they still were capable of recovering the clonogenic growth. In both models, DNA image cytometry revealed a protracted arrest in mid-late S phase, premature mitosis, and mitotic slippage in...

The significance of systemic polyploidy in the resistance of cancer cells to therapy is becoming more and more recognised. This complex process is not fully understood. We noticed their similarity with the primitive life-cycles of Entamoeba. The multi-lined populations of Entamoeba comprise a dominant mitotically cycling vegetative fraction and a m...

Accelerated senescence of cancer stem cells (CSCs) represents an adaptive response allowing withstand cell death. TP53, the pivotal tumor suppressor plays an important role in this process by inducing a prolonged dual state with senescence and self-renewal as potential outcomes. Molecularly, this is achieved by activating both OCT4A (POU5F1) and p2...

Cancer stem cells are believed to be responsible for radio- and chemoresistance of malignant tumors. In vitro studies demonstrate that ionizing radiation is capable of reprogramming cancer cells from non-stem state into stem state [1, 2]. Moreover, the embryonic stemness cassette was found to be expressed in tumor cells (including breast cancer cel...

The role of the nucleolus and autophagy in maintenance of nuclear integrity is poorly understood. In addition, the mechanisms of nuclear destruction in cancer cells senesced after conventional chemotherapy are unclear. In an attempt to elucidate these issues, we studied teratocarcinoma PA1 cells treated with Etoposide (ETO), focussing on the nucleo...

Survival of tumor cells after genotoxic damage, in particular those lacking TP53, requires a sophisticated series of cellular processes and ultrastructural reorganizations. Together these operations help to overcome the paradox between cellular senescence, high levels of DNA damage and the renewal of stemness. Recently we reported that autophagic c...

Survival of tumor cells after genotoxic damage, in particular those lacking TP53, requires a sophisticated series of cellular processes and ultrastructural reorganizations. Together these operations help to overcome the paradox between cellular senescence, high levels of DNA damage and the renewal of stemness. Recently we reported that autophagic...

Background A fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization. Principal Fin...

Complete sandpile transitional analyses of RNA-Seq data (RPKM): Complete sandpile transitional analyses of RNA-Seq data (RPKM) for A) human and B) mouse embryo development from the zygote stage, and C) T helper 17 cell differentiation from naïve CD4+ T cells. Random human and mouse expression matrixes (A and B: last panels), (i,j) (i: number of tim...

The genuineness of the power-law scaling and the existence of collective behavior of gene expression in power-law scaling: We demonstrate that i) the power-law scaling in the scaling divergent behavior (e.g., Fig 4A) is not a statistical artifact and ii) the dynamics of the collective behavior of gene expression exist through interactions among gen...

The timing of the genome-state change through the erasure of an initial-state criticality: The timing of the genome-state change occurs at the erasure of an initial-state criticality. This Fig demonstrates that the timing of the genome-state change does not vary with the choice of an initial state (t0) for A) DMSO-stimulated HL-60 cells (cell popul...

The dependence of cancer on overexpressed c-MYC and its predisposition for polyploidy represents a double puzzle. We address this conundrum by cross-species transcription analysis of c-MYC interacting genes in polyploid vs. diploid tissues and cells, including human vs. mouse heart, mouse vs. human liver and purified 4n vs. 2n mouse decidua cells....