To explore the possible mechanism of KLK11 in regulating the proliferation of ESCC, the expression of the related factors in Wnt/β-catenin pathway and cell cycle-mediated factors, such as GSK-3β/p-GSK-3β, β-catenin, Ki67, p-Rb/Rb, CDK6, CDK4 and Cyclin D1, were determined.
Moreover, we observed that triptolide induced ESCC cell cycle arrest at the G1/S phase and apoptosis through cyclin D1-CDK4/6 regulation and caspases activation.
Our findings reveal a molecular basis for cancer therapy through targeting glutaminolysis and mitochondrial respiration in ESCC with dysregulated Fbxo4-cyclin D1 axis as well as cancers resistant to CDK4/6 inhibitors.
Xanthohumol also decreased expression of cyclin D1 and increased the levels of cleaved caspase-3, -7 and -PARP as well as Bax, Bim<sub>s</sub> and cytochrome c in ESCC cells by downregulating AKT signaling targets, including glycogen synthase kinase 3 beta (GSK3β), mammalian target of rapamycin, and ribosomal protein S6 (S6K).
Here we report that entinostat reversed cisplatin resistance in ESCC both in vitro and in vivo by induction of apoptosis and inhibition of cell proliferation, accompanied by a decrease of multidrug resistance gene 1 (MDR1), P-Src, Mcl-1, Cyclin D1 and an increase of cleaved PARP.
Taken together, we propose that LBH589 inhibits ESCC cell proliferation mainly through inducing cell cycle arrest by increasing p21 and decreasing cyclin D1 in a p53-independent manner.
Therefore, <i>SOX2</i> might be considered as a potential prognostic indicator and a potential target for therapeutic targets in ESCC. p53 staining and combined p53 and Cyclin D1 expression had significantly unfavorable prognostic value for patients with ESCC.
Downregulation of HDAC2 expression evidently inhibited cell proliferation, arrested cell cycle at the G0/G1 phase and induced cell apoptosis in ESCC EC9706 cells, coupled with increased expression of p21 and Bax proteins and decreased expression of cyclin D1 and Bcl-2 proteins.
Mutations in TP53 and CDKN2A and copy number alterations in 11q (contains CCND1), 3q (contains SOX2), 2q (contains NFE2L2), and 9p (contains CDKN2A) were considered to be trunk variants; these were dominant mutations detected at high frequencies in clones of paired IEN and ESCC samples.
The present study reported that resveratrol exhibited a marked anti-proliferative effect on human esophageal squamous cell carcinoma (ESCC) cells by inducing cell cycle G<sub>0</sub>/G<sub>1</sub> phase arrest and cell death, which was associated with a decrease in the expression levels of cyclin D1 and an increase in cleaved PARP/cleaved caspase-3 expression levels.
CDK4/6 inhibitor-SHR6390 exerted potential antitumor activity against ESCC cell lines and xenografts, and evaluation of CDK6 and Cyclin D1 expressions might be helpful to select patients beneficial from SHR6390, which provided evidences for future clinical trials.
The overexpression of miR-375 downregulated MTDH (P<0.01), cyclin D1 (P<0.05) and vascular endothelial growth factor (P<0.01) expression, while upregulating epithelial cadherin (P<0.01) expression, which may account for its effect on ESCC cell proliferation and invasion.
Further investigation in the effect of miR-503 on ESCC cell proliferation, migration, and invasion showed that enhanced expression of miR-503 inhibited ESCC aggressive phenotype and overexpression of CCND1 reversed the effect of miR-503-mediated ESCC cell aggressive phenotype.
These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification.
To analyze the relationship between cysteine-rich 61 (Cyr61) and target genes of Wnt/β-catenin pathway (CCND1 and MYC) in 40 esophageal squamous cell carcinoma (ESCC) tissue specimens.
Mutations in FBXO4, F-box specificity factor that directs SCF-mediated ubiquitylation of cyclin D1, occur in ESCC with concurrent overexpression of cyclin D1 suggesting a potential tumor suppressor role for FBXO4.
This study aims to analyze the combined prognostic significance of cyclinD1 (CCND1) DNA amplification and the co-alteration of CCND1/pRb/ppRB in patients with esophageal squamous cell carcinoma.