p21<sup>cip1/waf1</sup> mediates various biological activities by sensing and responding to multiple stimuli, via p53-dependent and independent pathways. p21 is known to act as a tumor suppressor mainly by inhibiting cell cycle progression and allowing DNA repair.
Greater protein expression was detected for FGFR3, PI3Kp110α, PI3KClassIII, cyclins D1 and D3 and p21Waf1/Cip1 in the tumour tissue than in the healthy mucosa.
DEK significantly upregulated the expression levels of pro-apoptotic proteins such as cleaved caspase-3, cleaved caspase-9, cleaved PARP, p53, Bax, and tumor suppressor p21<sup>Cip1/Waf1</sup>, downregulated the levels of cell cycle regulating proteins such as cyclinD1, CDK2, and CDK4 and carcinogenic proteins such as EGFR and COX-2, and suppressed the activation of Akt.
Although known to induce cellular senescence, an important tumour suppressor mechanism, mutation of CDKN1A - the gene encoding p21 (also known as WAF1 or CIP1) - is rare in human cancers.
Through gain- and loss-of-function experiments, we demonstrated that the DRAK1 expression level regulated TGF-β1-induced transcriptional activity and expression of the tumor suppressor gene p21(Waf1/Cip1).
In cells expressing high levels of tumor suppressor p21WAF1/Cip1, it represses E2F1-mediated transcription, leading to down-regulation of multiple E2F1 target genes encoding for S-phase specific proteins, epigenetic modulators, and miRNAs (e.g. miR-15/16), and thereby stalling progression through the S-phase of cell cycle.
This new and unprecedented evidence for a link between SdhD dysfunction and p21(WAF1/Cip1) will open new avenues for the study of the mechanisms that cause tumors in Sdh mutants.
Immunohistochemistry (IHC) revealed decreased levels of Cul4A-associated proteins p21(CIP1) and tumour suppressor p19(ARF) in the lung tumours, suggesting that Cul4A regulated their expression in these tumours.
AMPK is a key effector of the tumor suppressor liver kinase B 1 (LKB1) which inhibits the cellular growth mediator mammalian target of rapamycin (mTOR) and activates checkpoint mediators such as p53 and the cyclin dependent kinase inhibitors p21(cip1) and p27(kip1).
These bioactive components have the ability to block UV-induced DNA hypermethylation and histone modifications in the skin required for the silencing of tumor suppressor genes (e.g.Cip1/p21, p16(INK4a) ).
Taken together, these results suggest that the p21(cip1) - and p27(kip1) -associated signaling pathways might be involved in the TB-induced anti-proliferation in KB cells.In vivo, TB (50 mg/kg, i.p.) significantly inhibited the KB tumor size.
Dietary administration of GSPs (0.5%, w/w) in supplementation with AIN76A control diet inhibited the growth of SCC1 tumor xenografts in athymic nude mice, which was associated with: (i) inhibition of cell proliferation, (ii) induction of apoptosis of tumor xenograft cells, (iii) decreased expression of cyclins and Cdks, (iv) decreased expression of EGFR, and (v) increased expression of Cip1/p21 and Kip1/p27 proteins and their increased binding to Cdks in tumor xenograft samples.
Inhibition of Notch3 signalling induces rhabdomyosarcoma cell differentiation promoting p38 phosphorylation and p21(Cip1) expression and hampers tumour cell growth in vitro and in vivo.
Both of p21(WAF1/Cip1)and TGF-β1's expression correlated with tumor differentiations. miR-221's upregulation and p27(Kip1)'s downregulation were significantly associated with tumor stages and metastasis.
This phenomenon is associated with a reduction in CDKs 4/2 (cyclin-dependent kinases) and cyclins E and D1 expression and an accumulation of p21(Waf1/Cip1) (a cyclin-dependent kinase inhibitor) and p53 (a tumor-suppressing protein).
Thus, our results suggest that KLF4 may function as a tumor suppressor in the skin and that the deregulated expression of KLF4 in the context of p21(Waf1/Cip1) and cyclin D1 expression may be involved in skin tumorigenesis.
We found that depletion of SPARC induces G2/M cell cycle arrest and tumor growth inhibition with activation of p53 and induction of p21(Cip1/Waf1) acting as a checkpoint, preventing efficient mitotic progression.
Re-expression of GATA4 in human GBM cell lines, primary cultures, and brain tumor-initiating cells suppressed tumor growth in vitro and in vivo through direct activation of the cell cycle inhibitor P21(CIP1), independent of TP53.
No correlations regarding protein expression and clinicopathological characteristics were observed; down-regulation of expression of P21(CIP1) with low (I-II) tumor stage (p=0.0777), and older age (>50 years old) with negative or mislocalization of P27(KIP1) (p=0.0922) were of borderline the statistical significance.