Cancer Stemness: p53 at the Wheel

Ghatak, Dishari; Ghosh, Damayanti Das; Roychoudhury, Susanta

doi:10.3389/fonc.2020.604124

Cited by 42 publications

(38 citation statements)

References 266 publications

(355 reference statements)

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“…Our previous study also demonstrated that the interaction between CCL21/CCR7 can regulate EMT and cell stemness [ 13 ]. Tumor cells with enhanced stemness possess stronger self-renewal ability and tumorigenicity [ 14 ]. However, whether FOXD1 participates in regulating EMT and stemness in OSCC remains unknown at present.…”

Section: Introductionmentioning

confidence: 99%

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

et al. 2021

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Background Epithelial-mesenchymal transition (EMT) and cell stemness are implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Revealing the intrinsic regulatory mechanism may provide effective therapeutic targets for OSCC. Results In this study, we found that Forkhead box D1 (FOXD1) was upregulated in OSCC compared with normal samples. Patients with a higher FOXD1 expression had a poorer overall survival and disease-free survival. Immunohistochemical staining results showed that FOXD1 expression was related to the clinical stage and relapse status of OSCC patients. When FOXD1 expression was knocked down in CAL27 and SCC25 cells, the migration, invasion, colony formation, sphere formation, and proliferation abilities decreased. Moreover, EMT and stemness-related markers changed remarkably, which indicated that the EMT process and cell stemness were inhibited. Conversely, overexpression of FOXD1 promoted EMT and cell stemness. Further study demonstrated that FOXD1 could bind to the promoter region and activate the transcription of SNAI2. In turn, the elevated SNAI2 affected EMT and cell stemness. An in vivo study showed that FOXD1-overexpressing CAL27 cells possessed a stronger tumorigenic ability. Conclusions Our findings revealed a novel mechanism in regulating EMT and cell stemness and proposed FOXD1 as a potential marker for the diagnosis and treatment of OSCC.

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Section: Introductionmentioning

confidence: 99%

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

et al. 2021

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“…Before ESC differentiation, the expression level of P53 is very low in human ESCs, and HDM2 and TRIM24, two negative regulators of P53, trigger P53 degradation. Active P53 in turn promotes the expression of a cell cycle regulator P21, which slows down human ESC by prolonging the cell cycle gap (G1) phase (Jain et al, 2012;Ghatak et al, 2021). In addition, many studies have shown that P53 has many downstream target genes that play regulatory roles, including some non-coding RNAs, such as miR-34a and miR-145, currently being identified as regulated by P53 (Hermeking, 2007;Jain et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

WDR36 Safeguards Self-Renewal and Pluripotency of Human Extended Pluripotent Stem Cells

Yao

Zhang

et al. 2022

Front. Genet.

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Extended pluripotent stem cells (EPS cells) have unlimited self-renewal ability and the potential to differentiate into mesodermal, ectodermal, and endodermal cells. Notably, in addition to developing the embryonic (Em) lineages, it can also make an effective contribution to extraembryonic (ExEm) lineages both in vitro and in vivo. However, multiple mysteries still remain about the underlying molecular mechanism of EPS cells’ maintenance and developmental potential. WDR36 (WD Repeat Domain 36), a protein of 105 kDa with 14 WD40 repeats, which may fold into two β-propellers, participates in 18sRNA synthesis and P53 stress response. Though WDR36 safeguards mouse early embryonic development, that is, homozygous knockout of WDR36 can result in embryonic lethality, what role does WDR36 plays in self-renewal and differentiation developmental potential of human EPS cells is still a subject of concern. Here, our findings suggested that the expression of WDR36 was downregulated during human hEPS cells lost self-renewal. Through constructing inducible knockdown or overexpressing WDR36-human EPS cell lines, we found that WDR36 knockdown disrupted self-renewal but promoted the mesodermal differentiation of human EPS cells; however, overexpressing of WDR36 had little effect. Additionally, P53 inhibition could reverse the effects of WDR36 knockdown, on both self-renewal maintenance and differentiation potential of human EPS cells. These data implied that WDR36 safeguards self-renewal and pluripotency of human EPS cells, which would extend our understanding of the molecular mechanisms of human EPS cells’ self-renewal and differentiation.

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“…Third, in gastric CSCs, a higher expression level of FOXA2 is sustained by autophagy [ 129 ], which promotes cell proliferation and maintain CSC stemness [ 130 ], and overexpressing FOXA2 partially rescues the decreased self-renewal ability when autophagy is inhibited [ 129 ]. Finally, autophagy can augment cell stemness through degrading ubiquitinated TP53 [ 125 , 131 ]. All the studies mentioned above indicate that autophagy positively regulates CSC.…”

Section: Autophagy and Cancermentioning

confidence: 99%

The Emerging Roles of Autophagy in Human Diseases

Lei

Klionsky

2021

Biomedicines

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Autophagy, a process of cellular self-digestion, delivers intracellular components including superfluous and dysfunctional proteins and organelles to the lysosome for degradation and recycling and is important to maintain cellular homeostasis. In recent decades, autophagy has been found to help fight against a variety of human diseases, but, at the same time, autophagy can also promote the procession of certain pathologies, which makes the connection between autophagy and diseases complex but interesting. In this review, we summarize the advances in understanding the roles of autophagy in human diseases and the therapeutic methods targeting autophagy and discuss some of the remaining questions in this field, focusing on cancer, neurodegenerative diseases, infectious diseases and metabolic disorders.

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Cancer Stemness: p53 at the Wheel

Cited by 42 publications

References 266 publications

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

WDR36 Safeguards Self-Renewal and Pluripotency of Human Extended Pluripotent Stem Cells

The Emerging Roles of Autophagy in Human Diseases

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