EGF promotes mammalian cell growth by suppressing cellular senescence

Alexander, Peter; Yuan, Lifeng; Yang, Pengyuan; Sun, Tao; Chen, Rui; Xiang, Handan; Chen, Jiekai; Wu, Haoyu; Radiloff, Daniel R.; Wang, Xiaofan

doi:10.1038/cr.2014.141

Cited by 50 publications

(47 citation statements)

References 13 publications

(14 reference statements)

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“…The accumulated EGF release showed significantly higher rates in the case of A-PRF and A-PRF+ compared with PRF at most time points, particularly on day 10. EGF has previously been described as promoting cell growth [21], enhancing keratinocyte migration [23], inhibiting apoptosis under hypoxic conditions [24], and supporting reepithelization and skin healing [25,26]. Additionally, EGF supports the healing process of chronic wounds [27], nonhealing chronic wounds and ulcers, which are, for example, observed in diabetic patients known to lack the necessary growth factors to maintain the healing process [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, PRF matrices with an enhanced release of TGF-β1, as was the case for A-PRF and A-PRF+, could have a major influence on wound healing as a catalyzer of wound repair stages. In addition, this growth factor is known to stimulate fibroblast migration, enhance collagen synthesis and promote angiogenesis [21,22]. All of the latter characteristics are essential in the biomaterial-based regeneration process.…”

Section: Discussionmentioning

confidence: 99%

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Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: a proof of concept of LSCC (low speed centrifugation concept)

Bagdadi

Kubesch

et al. 2017

Eur J Trauma Emerg Surg

139

135

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Moreover, platelets were located homogenously throughout the matrix in the A-PRF and A-PRF+ groups, whereas platelets in PRF were primarily observed within the lower portion. Discussion the present results show an increase growthfactor release by decreased RCF. However, further studies must be conducted to examine the extent to which enhancing the amount and the rate of released growth factors influence wound healing and biomaterial-based tissue regeneration. Conclusion These outcomes accentuate the fact that with a reduction of RCF according to the previously LSCC (described low speed centrifugation concept), growth factor release can be increased in leukocytes and platelets within the solid PRF matrices.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: a proof of concept of LSCC (low speed centrifugation concept)

Bagdadi

Kubesch

et al. 2017

Eur J Trauma Emerg Surg

139

135

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“…In summary, our studies reveal an important role for AMPKα2 isoform in cell biology and connect two hallmarks of aging cells (Alexander et al, 2015; Lopez-Otin et al, 2013): cellular senescence and loss of proteostasis/proliferation capacity, which may be due to HBP1 elevation. Given the importance of AMPK in cellular senescence, these findings hold profound implications for understanding the molecular mechanisms by which AMPK functions as a promising suppressor of cellular senescence, as well as tissue/organ aging.…”

Section: Discussionmentioning

confidence: 72%

“…Here, we observed that AMPKα2 deletion in either young or old mice increases the number of senescent cells in the skin, while impeding the proliferative capacity evidenced by weaker staining of Ki-67. In addition, aged skin usually has reduced dermal thickness (Alexander et al, 2015; Branchet et al, 1990; Gambichler et al, 2006), whereas, AMPKα2-deleted mice have increased dermal thickness (Fig. 6).…”

Section: Discussionmentioning

confidence: 99%

Absence of AMPKα2 accelerates cellular senescence via p16 induction in mouse embryonic fibroblasts

Ding

Chen

Okon

et al. 2016

The International Journal of Biochemistry & Cell Biology

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Emerging evidence suggests that activation of adenosine monophosphate-activated protein kinase (AMPK), an energy gauge and redox sensor, delays aging process. However, the molecular mechanisms by which AMPKα isoform regulates cellular senescence remain largely unknown. The aim of this study was to determine if AMPKα deletion contributes to the accelerated cell senescence by inducing p16INK4A (p16) expression thereby arresting cell cycle. The markers of cellular senescence, cell cycle proteins, and reactive oxygen species (ROS) were monitored in cultured mouse embryonic fibroblasts (MEFs) isolated from wild type (WT, C57BL/6J), AMPKα1, or AMPKα2 homozygous deficient (AMPKα1−/−, AMPKα2−/−) mice by Western blot and cellular immunofluorescence staining, as well as immunohistochemistry (IHC) in skin tissue of young and aged mice. Deletion of AMPKα2, the minor isoform of AMPKα, but not AMPKα1 in high-passaged MEFs led to spontaneous cell senescence demonstrated by accumulation of senescence-associated-β-galactosidase (SA-β-gal) staining and foci formation of heterochromatin protein 1 homolog gamma (HP1γ). It was shown here that AMPKα2 deletion upregulates cyclin-dependent kinase (CDK) inhibitor, p16, which arrests cell cycle. Furthermore, AMPKα2 null cells exhibited elevated ROS production. Interestingly, knockdown of HMG box-containing protein 1 (HBP1) partially blocked the cellular senescence of AMPKα2-deleted MEFs via the reduction of p16. Finally, dermal cells senescence, including fibroblasts senescence evidenced by the staining of p16, HBP1, and Ki-67, in the skin of aged AMPKα2−/− mice was enhanced when compared with that in wild type mice. Taken together, our results suggest that AMPKα2 isoform plays a fundamental role in anti-oxidant stress and anti-senescence.

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“…Significantly, some next-generation compounds have shown efficacy in inhibiting RTK isoforms associated with resistance, including EGFR T790M [26]. However, since EGFR activity is important for normal tissue homeostasis [27], the use of many next-generation RTK inhibitors appears to be limited by toxicity stemming from the irreversible inhibition of wild-type EGFR in normal cells. Because of this, efforts are currently underway to develop inhibitors preferentially targeting T790M over wild-type EGFR [28].…”

Section: Future Prospects For Treatmentmentioning

confidence: 99%

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

Alexander

Wang

2015

Front. Med.

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Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

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EGF promotes mammalian cell growth by suppressing cellular senescence

Cited by 50 publications

References 13 publications

Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: a proof of concept of LSCC (low speed centrifugation concept)

Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: a proof of concept of LSCC (low speed centrifugation concept)

Absence of AMPKα2 accelerates cellular senescence via p16 induction in mouse embryonic fibroblasts

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

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