2022年9月7日 · Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell...

【摘要】 抑癌基因p16ink4a在特异地抑制 CDK4及CDK6在控制细胞生长、 抑制肿瘤发生、 促进细胞衰老等方面发挥关键生物学作用, 该基因失活后造成了细胞周期调控失常,使得细胞异常增殖,造成了肿瘤发生、 发展, 本文就近几年来相关它在染色体上定位、 结构以及在 ...

Deregulation of the p16(INK4a)-Cdk4/6-Rb pathway is commonly detected in patients with glioblastoma multiforme (GBM) and is a rational therapeutic target. Here, we characterized the p16(INK4a)-Cdk4/6-Rb pathway in the Mayo panel of GBM xenografts, established from primary tissue samples from patient …

2021年11月1日 · We demonstrate that Pos3AaTM-mCherry-p16 fusion crystals can efficiently deliver p16 protein, a CDK4/6 inhibitor frequently inactivated in human cancers, into p16-deficient UM-SCC-22A cells, where it promotes significant G1 cell cycle arrest and cell growth inhibition.

2011年7月14日 · The p16 INK4a-Cdk4-Rb pathway controlling cell-cycle progression is commonly hyper-activated in patients with GBM and is a potentially important therapeutic target. 14 In 2 recent whole genome analyses of GBM tumors, disruption of the p16-Cdk4-Rb pathway was observed in >70% of patients, 1, 2 and similar to these studies, all GBM xenografts ...

2023年2月18日 · Mechanistically, overexpression of p16 INK4a causes abnormal accumulation of reactive oxygen species (ROS) to induce autophagy, while scavenging ROS with N-acetylcysteine can alleviate autophagy and regulate p16 INK4a, CDK4/6, and CyclinD1 in a covering manner.

Palbociclib is a highly specific CDK4/6 inhibitor shown to inhibit cell cycle progression and promote cellular senescence. We conducted a phase 2 clinical trial of palbociclib in 19 previously-treated patients with advanced NSCLC. Only patients with p16-null staining by immunohistochemistry and documented tumor progression were eligible.

The p16(INK4a) tumor suppressor, whose expression is inhibited in a high number of cancers, binds to Cdk4/6 and inhibits phosphorylation of the retinoblastoma protein, forcing cells to remain in the G1 phase and therefore, arresting cell division.

2017年8月8日 · CDK4/6 inhibitors and CDK4 knockdown do not mimic effects of p16 on mitochondrial dynamics and respiration. p16 represses cell cycle progression through binding of CDK4/6, which inhibits Rb phosphorylation . We investigated whether p16-mediated modulation of mitochondrial dynamics was operating through this canonical CDK/Rb pathway by testing ...

Whereas P16 is able to bind to and suppress the transactivational activity of NF-κB, IκBα, a specific inhibitor of NF-κB, competes with P16 for CDK4 binding and inhibits CDK4-mediated phosphorylation of pRb as potently as P16 does .