The role of meiotic cohesin REC8 in chromosome segregation in γ irradiation-induced endopolyploid tumour cells

Ērenpreisa, Jekaterina; Cragg, Mark S.; Salmiņa, Kristīne; Hausmann, Michael; Scherthan, Harry

doi:10.1016/j.yexcr.2009.05.011

Cited by 68 publications

(84 citation statements)

References 56 publications

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“…Human REC8 has been shown to be present in endopolyploid TP53-deficient tumor cells induced by ionizing irradiation (64). It was previously proposed that REC8 functions in these cells to induce pseudomeiotic chromosome segregation events that enable them to survive genotoxic treatment, which might infer REC8 (and potentially other meiotic factors) can drive therapeutic resistance in tumors (64). A screen for human CT genes specifically associated with meiotic spermatocytes did not identify REC8, although it did identify other meiosis-specific cohesin genes, RAD21L1 and SMC1b (31).…”

Section: Activation Of Meiotic Functions In Cancer Cellsmentioning

confidence: 99%

Meiosis-like Functions in Oncogenesis: A New View of Cancer

McFarlane

Wakeman

2017

Cancer Research

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Cancer cells have many abnormal characteristics enabling tumors to grow, spread, and avoid immunologic and therapeutic destruction. Central to this is the innate ability of populations of cancer cells to rapidly evolve. One feature of many cancers is that they activate genes that are normally associated with distinct developmental states, including germ cell–specific genes. This has historically led to the proposal that tumors take on embryonal characteristics, the so called embryonal theory of cancer. However, one group of germline genes, not directly associated with embryonic somatic tissue genesis, is the one that encodes the specific factors to drive the unique reductional chromosome segregation of meiosis I, which also results in chromosomal exchanges. Here, we propose that meiosis I–specific modulators of reductional segregation can contribute to oncogenic chromosome dynamics and that the embryonal theory for cancer cell growth/proliferation is overly simplistic, as meiotic factors are not a feature of most embryonic tissue development. We postulate that some meiotic chromosome-regulatory functions contribute to a soma-to-germline model for cancer, in which activation of germline (including meiosis) functions drive oncogenesis, and we extend this to propose that meiotic factors could be powerful sources of targets for therapeutics and biomonitoring in oncology. Cancer Res; 77(21); 5712–6. ©2017 AACR.

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Section: Activation Of Meiotic Functions In Cancer Cellsmentioning

confidence: 99%

Meiosis-like Functions in Oncogenesis: A New View of Cancer

McFarlane

Wakeman

2017

Cancer Research

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“…Cohesion of sister centromeres by the meiotic cohesin Rec8 was found in ETC of a human lymphoma cell line undergoing reduction divisions after a period of intensive homologous DNA repair involving the mitotic/meiotic recombinases Rad51 and DMC1 (Ivanov et al, 2003;Erenpreisa et al, 2009;Ianzini et al, 2009).…”

Section: Meiotic-like Processes In Etcmentioning

confidence: 99%

“…Many meiotic genes have now been observed to be upregulated in genotoxically stressed lymphoma, HeLa and breast cancer human cell lines including MOS, REC8, SGO1 and SPO11 Kalejs et al, 2006;Ianzini et al, 2009;Erenpreisa et al, 2009). It is interesting to note then, that mutations in genes involved in homologous recombination, sister chromatid cohesion and spindle formation were amongst the few revealed as polyploidy-specific lethal in a large-scale genetic screen in yeast (Storchovaé t al., 2006).…”

Section: Meiotic-like Processes In Etcmentioning

confidence: 99%

MOS, aneuploidy and the ploidy cycle of cancer cells

Ērenpreisa

Cragg

2010

Oncogene

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After DNA or spindle damage, p53-defective tumor cells undergo a complex cycle of reversible polyploidy. How this process occurs and more importantly, why, has recently become the focus of several research groups, prompting this review in which we discuss two related phenomena that accompany the reversible polyploidy of tumor cells: the induction of meiosis genes such as MOS and the decrease in genomic instability observed during the reversion from polyploidy to para-diploidy. The reversible polyploidy likely provides the means through which the balance between increased chromosome instability (CIN), driving genetic variation and decreased CIN, necessary for perpetuating these malignant clones, is maintained. These concepts are integrated with recent findings that many meiotic and self-renewal genes become activated during reversible polyploidy and lead us to the hypothesis that tumor cell immortality may be achieved through germline-like transmission.

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“…In irradiated lymphomas and HeLa cells this nondegraded cyclin B1 was found to be sustained by activated Mos kinase [39]. Some additional activators of meiotic prophase were also revealed [40,41] indicating a possible trigger from the mitotic DNA damage checkpoint into a meiotic prophase-like state with its more efective recombination checkpoint. Potentially, this meiosis-like molecular seting allows CSCs to tolerate both DNA damage and tetraploidy and use this compartment for DNA repair by homologous recombination [14,42].…”

Section: Biological Features Of Cell Senescence: What Is Clear and Whmentioning

confidence: 95%

Accelerated Senescence of Cancer Stem Cells: A Failure to Thrive or a Route to Survival?

Ērenpreisa¹,

Salmiņa²,

Cragg³

2017

Senescence - Physiology or Pathology

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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 p21CIP1. OCT4A suppresses the excessive activity of p21 preventing the immediate precipitation of apoptosis or terminal senescence. It persists as long as suicient cellular energy remains; generated through autophagy, itself sequestrating p16INK4A in the cytoplasm. As such, autophagic capacity is the botleneck of these TP53-dependent senescence reversal processes, as well terminal senescence will follow if DNA damage is not ultimately repaired. In TP53 mutants the CSC-like state is boosted by stressed cells overcoming the tetraploidy barrier.These cells acquire additional DNA repair capacity through mitotic slippage and entrance to a sequence of ploidy cycles, allowing repair and sorting DNA damage, ultimately facilitating the genesis of mitotically competent daughter cells following inal depolyploidisation. Again, autophagy is required to fuel this process. More detailed knowledge of these arcane processes anticipates the provision of anti-cancer drug targets, such as AURORA B kinase and Survivin, which ensure mitotic slippage and the continuity of ploidy cycles.

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The role of meiotic cohesin REC8 in chromosome segregation in γ irradiation-induced endopolyploid tumour cells

Cited by 68 publications

References 56 publications

Meiosis-like Functions in Oncogenesis: A New View of Cancer

Meiosis-like Functions in Oncogenesis: A New View of Cancer

MOS, aneuploidy and the ploidy cycle of cancer cells

Accelerated Senescence of Cancer Stem Cells: A Failure to Thrive or a Route to Survival?

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