https://transhumanist.ru/index.php?action=history&feed=atom&title=CSN2CSN2 - История изменений2026-08-17T10:34:11ZИстория изменений этой страницы в викиMediaWiki 1.43.6https://transhumanist.ru/index.php?title=CSN2&diff=6280&oldid=prevOdysseusBot: Новая страница: «Beta-casein precursor [CASB] ==Publications== {{medline-entry |title=Autophagic homeostasis is required for the pluripotency of cancer stem cells. |pubmed-url=h...»2021-05-12T15:21:04Z<p>Новая страница: «Beta-casein precursor [CASB] ==Publications== {{medline-entry |title=Autophagic homeostasis is required for the pluripotency of cancer stem cells. |pubmed-url=h...»</p>
<p><b>Новая страница</b></p><div>Beta-casein precursor [CASB]<br />
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==Publications==<br />
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{{medline-entry<br />
|title=Autophagic homeostasis is required for the pluripotency of cancer stem cells.<br />
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27929731<br />
|abstract=Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD synthesis pathway [[NAMPT]] (nicotinamide phosphoribosyltransferase) and the transcription factor [[POU5F1]]/OCT4 (POU class 5 homeobox 1). First, our data show that the pharmacological inhibition and knockdown (K ) of [[NAMPT]] or the K of [[POU5F1]] in human CSCs significantly decreased the expression of pluripotency markers [[POU5F1]], [[NANOG]] (Nanog homeobox) and [[SOX2]] (SRY-box 2), and upregulated the differentiation markers [[TUBB3]] (tubulin β 3 class III), [[CSN2]] (casein β), [[SPP1]] (secreted phosphoprotein 1), [[GATA6]] (GATA binding protein 6), T (T brachyury transcription factor) and [[CDX2]] (caudal type homeobox 2). Interestingly, these pluripotency-regulating effects of [[NAMPT]] and [[POU5F1]] were accompanied by contrasting levels of autophagy, wherein [[NAMPT]] K promoted while [[POU5F1]] K inhibited the autophagy machinery. Most importantly, any deviation from the basal level of autophagy, either increase (via rapamycin, serum starvation or Tat-beclin 1 [Tat-BECN1] peptide) or decrease (via [[ATG7]] or [[ATG12]] K ), strongly decreased the pluripotency and promoted the differentiation and/or senescence of CSCs. Collectively, these results uncover the link between the NAD biosynthesis pathway, CSC transcription factor [[POU5F1]] and pluripotency, and further identify autophagy as a novel regulator of pluripotency of CSCs.<br />
|mesh-terms=* Animals<br />
* Autophagy<br />
* Beclin-1<br />
* Cell Differentiation<br />
* Cell Proliferation<br />
* Cell Survival<br />
* Cellular Senescence<br />
* Cytokines<br />
* Doxorubicin<br />
* Homeostasis<br />
* Mice<br />
* Models, Biological<br />
* Neoplastic Stem Cells<br />
* Nicotinamide Phosphoribosyltransferase<br />
* Octamer Transcription Factor-3<br />
* PTEN Phosphohydrolase<br />
* Phosphorylation<br />
* Pluripotent Stem Cells<br />
* Proto-Oncogene Proteins c-akt<br />
* Signal Transduction<br />
* Sirolimus<br />
* TOR Serine-Threonine Kinases<br />
|keywords=* POU5F1/Oct4<br />
* autophagy<br />
* cancer stem cells<br />
* differentiation<br />
* pluripotency<br />
* senescence<br />
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324853<br />
}}</div>OdysseusBot