Reprogramming and Carcinogenesis—Parallels and Distinctions

Wasik, Agata M.; Grabarek, Jerzy; Pantovic, Aleksandar; Cieślar-Pobuda, Artur; Asgari, Hamid; Bundgaard‐Nielsen, Caspar; Rafat, Mehrdad; Dixon, Ian M.C.; Ghavami, Saeid; Łos, Marek

doi:10.1016/b978-0-12-800097-7.00005-1

Cited by 49 publications

(42 citation statements)

References 176 publications

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“…1,2 The origin of CSCs is still debated. They may either originate from normal (tissue) stem cells or form in a process similar to reprogramming (dedifferentiation).…”

Section: Introductionmentioning

confidence: 99%

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1

et al. 2015

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Cancer stem-like cells (CSCs) are a rare subpopulation of cancer cells capable of propagating the disease and causing cancer recurrence. In this study, we found that the cellular localization of PKB/Akt kinase affects the maintenance of CSCs. When Akt tagged with nuclear localization signal (Akt-NLS) was overexpressed in SKBR3 and MDA-MB468 cells, these cells showed a 10-15% increase in the number of cells with CSCs enhanced ALDH activity and demonstrated a CD44 CHigh /CD24 ¡Low phenotype. This effect was completely reversed in the presence of Aktspecific inhibitor, triciribine. Furthermore, cells overexpressing Akt or Akt-NLS were less likely to be in G0/G1 phase of the cell cycle by inactivating p21 Waf1/Cip1 and exhibited increased clonogenicity and proliferation as assayed by colony-forming assay (mammosphere formation). Thus, our data emphasize the importance the intracellular localization of Akt has on stemness in human breast cancer cells. It also indicates a new robust way for improving the enrichment and culture of CSCs for experimental purposes. Hence, it allows for the development of simpler protocols to study stemness, clonogenic potency, and screening of new chemotherapeutic agents that preferentially target cancer stem cells. Summary: The presented data, (i) shows new, stemness-promoting role of nuclear Akt/PKB kinase, (ii) it underlines the effects of nuclear Akt on cell cycle regulation, and finally (iii) it suggests new ways to study cancer stem-like cells.

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“…1,2 The origin of CSCs is still debated. They may either originate from normal (tissue) stem cells or form in a process similar to reprogramming (dedifferentiation).…”

Section: Introductionmentioning

confidence: 99%

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1

et al. 2015

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“…Like in some other diseases (Likus et al 2016a), it is however sometimes difficult to clearly associate the given pathogen with cancer etiology. Many viruses preferentially or exclusively replicate in dividing cells; hence, their components are potentially becoming an important source/inspiration in the search of drugs that preferentially target cancer stem cells (AkbariBirgani et al 2016;Farahani et al 2014;Wasik et al 2014). Beside viral methods, some clinically tested as well as new drugs with preferential toxicity towards cancer stem cells are increasingly becoming available (Jangamreddy et al 2013;Likus et al 2016b;Moosavi et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Human Gyrovirus-Apoptin Interferes with the Cell Cycle and Induces G2/M Arrest Prior to Apoptosis

Chaabane

Ghavami

Małecki

et al. 2017

Arch. Immunol. Ther. Exp.

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“…Another problem is the long period for full iPSC reprogramming and the high cells proliferation rates associated with a greater chance of developing cancer. 71 Takahashi and Yamanaka suggest considering using iPSC with allogeneic transplantation in regenerative medicine, which would improve the effectiveness of the treatment of certain diseases such as spinal cord injury, which requires quick treatment without waiting for the time taken for reprogramming. 11 Furthermore, there is a need for better understanding of how the reprogramming interventions influence the epigenetic memory of the reprogrammed cells.…”

Section: Resultsmentioning

confidence: 99%

Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine

Gomes

Costa

Santos

et al. 2017

Rev. Assoc. Med. Bras.

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Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed into an embryonic-like pluripotent state by the expression of specific transcription factors. iPSC technology is expected to revolutionize regenerative medicine in the near future. Despite the fact that these cells have the capacity to self-renew, they present low efficiency of reprogramming. Recent studies have demonstrated that the previous somatic epigenetic signature is a limiting factor in iPSC performance. Indeed, the process of effective reprogramming involves a complete remodeling of the existing somatic epigenetic memory, followed by the establishment of a "new epigenetic signature" that complies with the new type of cell to be differentiated. Therefore, further investigations of epigenetic modifications associated with iPSC reprogramming are required in an attempt to improve their self-renew capacity and potency, as well as their application in regenerative medicine, with a new strategy to reduce the damage in degenerative diseases. Our review aimed to summarize the most recent findings on epigenetics and iPSC, focusing on DNA methylation, histone modifications and microRNAs, highlighting their potential in translating cell therapy into clinics.

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Reprogramming and Carcinogenesis—Parallels and Distinctions

Cited by 49 publications

References 176 publications

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1

Human Gyrovirus-Apoptin Interferes with the Cell Cycle and Induces G2/M Arrest Prior to Apoptosis

Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine

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Reprogramming and Carcinogenesis—Parallels and Distinctions

Cited by 49 publications

References 176 publications

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21Waf1/Cip1and p27kip1

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21Waf1/Cip1and p27kip1

Human Gyrovirus-Apoptin Interferes with the Cell Cycle and Induces G2/M Arrest Prior to Apoptosis

Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine

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Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1