Related Experiment Video

Updated: Aug 7, 2026

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts
10:04

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts

Published on: January 8, 2017

TPPII promotes genetic instability by allowing the escape from apoptosis of cells with activated mitotic checkpoints

Vaia Stavropoulou1, Vanessa Vasquez, Biancastella Cereser

  • 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Biochemical and Biophysical Research Communications
|June 10, 2006
PubMed

Insights

Overexpression of trans-endothelial proteinase inhibitor II (TPPII) accelerates cell cycle and promotes genetic instability in cancer cells. TPPII enables cancer cells to survive mitotic damage, promoting malignant growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Trans-endothelial proteinase inhibitor II (TPPII) overexpression is linked to accelerated growth and genetic instability in malignant cells.
  • TPPII's role in maintaining genetic instability and its impact on cell cycle regulation require further elucidation.

Purpose of the Study:

  • To investigate the functional role of TPPII in cell cycle progression, mitosis, and cell survival.
  • To determine how TPPII influences mitotic arrest, polyploidy, and apoptosis in cancer cells.

Main Methods:

  • Utilizing HEK293 cells with TPPII overexpression and TPPII knockdown via shRNA interference.
  • Assessing cell cycle length, mitotic progression, polyploidy, and apoptosis resistance.

Main Results:

  • TPPII overexpression significantly reduced cell cycle and mitosis duration, while knockdown caused cell growth slowdown and mitotic defects.
  • TPPII-overexpressing cells evaded spindle poison-induced mitotic arrest, exhibited polyploidy, and showed resistance to p53-induced apoptosis.
  • TPPII overexpression correlated with increased levels of Inhibitor of Apoptosis Proteins (IAPs).

Conclusions:

  • TPPII promotes malignant cell growth by facilitating exit from mitosis and survival of cells with mitotic spindle damage.
  • TPPII appears to be a critical factor in the induction and/or maintenance of genetic instability in cancer cells.
  • TPPII contributes to cancer progression by enhancing cell survival despite severe mitotic errors.

More Related Videos

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel08:29

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel

Published on: May 14, 2018

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Related Concept Videos

Abnormal Proliferation02:23

Abnormal 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...
DNA Damage can Stall the Cell Cycle02:36

DNA 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...
DNA Damage Can Stall the Cell Cycle02:36

DNA 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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...