Polyploid tumour cells elicit paradiploid progeny through depolyploidizing divisions and regulated autophagic degradation

Ērenpreisa, Jekaterina; Salmiņa, Kristīne; Huna, Anda; Kosmacek, Elizabeth A.; Cragg, Mark S.; Ianzini, Fiorenza; Anisimov, A. P.

doi:10.1002/j.1095-8355.2011.tb02107.x

Cited by 8 publications

(11 citation statements)

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“…Indeed, it is reasonable to suggest that the unique mechanism of acquired resistance to metformin has opposing roles in growth and metastatic dissemination, while refractoriness to metformin limits breast cancer cell growth, likely due to an aberrant mitotic/cytokinetic machinery and accelerated autophagy, it notably increases the potential of metastatic dissemination by amplifying the number of pro-migratory and stemness inputs via the activation of a significant number of proteases and EMT regulators. Future studies should unambiguously elucidate whether our findings using supra-physiological concentrations of metformin mechanistically recapitulate the processes through which the induction of a migratory-stemness cellular state paradoxically occurs in a polyploid, senescent-autophagic scenario [102][103][104][105] that is triggered by the chronic metabolic stresses that commonly occur during cancer development and after treatment with cancer drugs.…”

Section: P Value Ratiomentioning

confidence: 81%

Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile

et al. 2014

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Section: P Value Ratiomentioning

confidence: 81%

Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile

et al. 2014

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“…This sorting of the DNA damage through micronucleation was observed by us in several tumor cell line models after diferent kinds of genotoxic treatments as exempliied in Figure 6 (A-C). The autophagic elimination of large DNA portions or whole sub-nuclei with damaged DNA was also observed (Figure 6D) [62,68,69] as another intriguing feature of the late post-damage events of genotoxically treated TP53 mutants.…”

Section: The Role Of Autophagy In Preventing Terminal Senescencementioning

confidence: 77%

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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“…63,64 Furthermore, evidence shows that, following chemotherapy, the remainder of the giant cellular content, including extra-DNA and cytoplasmic material, seems to be cleared by autophagy. 65…”

Section: Reverse Ploidymentioning

confidence: 99%

Repopulation of Ovarian Cancer Cells after Chemotherapy

Telleria

2013

Cancer�Growth�Metastasis

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The high mortality rate caused by ovarian cancer has not changed for the past thirty years. Although most patients diagnosed with this disease respond to cytoreductive surgery and platinum-based chemotherapy and undergo remission, foci of cells almost always escape therapy, manage to survive, and acquire the capacity to repopulate the tumor. Repopulation of ovarian cancer cells that escape front-line chemotherapy, however, is a poorly understood phenomenon. Here I analyze cancer-initiating cells, transitory senescence, reverse ploidy, and cellular dormancy as putative players in ovarian cancer cell repopulation. Under standard of care, ovarian cancer patients do not receive treatment between primary cytotoxic therapy and clinical relapse; understanding the mechanisms driving cellular escape from chemotherapy should lead to the development of low toxicity, chronic treatment approaches that can be initiated right after primary therapy to interrupt cell repopulation and disease relapse by keeping it dormant and, therefore, subclinical.

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Polyploid tumour cells elicit paradiploid progeny through depolyploidizing divisions and regulated autophagic degradation

Cited by 8 publications

References 0 publications

Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile

Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile

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

Repopulation of Ovarian Cancer Cells after Chemotherapy

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