Related Experiment Video
Updated: May 19, 2026
10:04
Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts
Published on: January 8, 2017
Polyploidy road to therapy-induced cellular senescence and escape
Qin Wang1, Peter C Wu, David Z Dong
1Seattle Institute for Biomedical and Clinical Research, VA Puget Sound Health Care System, Seattle, WA 98108, USA. proteins@hotmail.com
International Journal of Cancer
|September 5, 2012
Summary
Therapy-induced cellular senescence (TCS) can reverse, leading to tumor progression. In advanced non-small cell lung cancer, TCS markers predict poor outcomes, highlighting Cdk1
Area of Science:
- Oncology
- Cell Biology
- Cancer Therapeutics
Background:
- Therapy-induced cellular senescence (TCS) is a reversible cell cycle arrest in cancer cells responding to chemotherapy and radiation.
- Reversible TCS contributes to tumor progression, mirroring clinical challenges in advanced cancers.
- Understanding TCS mechanisms is crucial for improving cancer treatment efficacy.
Purpose of the Study:
- To investigate the prognostic significance of in vivo TCS markers in locally advanced non-small cell lung cancer (NSCLC) following neoadjuvant therapy.
- To elucidate molecular pathways governing TCS and cell cycle escape, focusing on Cdk1.
- To determine the role of Cdk1 in apoptosis interference and polyploid senescent cell formation during TCS.
Main Methods:
- Clinicopathological study of patients with locally advanced NSCLC.
- Analysis of in vivo TCS markers post-neoadjuvant therapy.
- Investigation of Cdk1 deregulation, apoptosis, and polyploidization in senescent cells.
Main Results:
- In vivo TCS markers after neoadjuvant therapy were associated with adverse clinical outcomes in NSCLC patients.
- Aberrant Cdk1 expression interferes with apoptosis and promotes polyploid senescent cell formation during TCS.
- The Cdk1 pathway is differentially modulated by p21 and p27 during TCS.
Conclusions:
- TCS markers are prognostic indicators of adverse outcomes in NSCLC treated with neoadjuvant therapy.
- Cdk1 plays a critical role in promoting polyploid senescent cells and interfering with apoptosis, facilitating escape from TCS.
- Targeting the Cdk1 pathway, modulated by p21 and p27, may offer therapeutic strategies to overcome TCS-mediated tumor progression.
Related Concept Videos
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
01:21Nondisjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...
01:29Nondisjunction
During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...