PIK3R3 inhibits cell senescence through p53/p21 signaling

Qianzhi Chen1,2, Xuling Sun1, Xuelai Luo1

  • 1Department of GI Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Cell Death & Disease
|September 25, 2020
PubMed

Insights

This study reveals that PIK3R3 protein inhibits cellular senescence in colorectal cancer by affecting the p53/p21 pathway. Inhibiting PIK3R3 may offer a new therapeutic strategy for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cellular senescence is a critical process that halts cell cycle progression, eliminating potentially harmful cells.
  • Inducing tumor cell senescence presents a promising strategy for cancer therapy.
  • The role of specific proteins in regulating senescence, particularly in colorectal cancer, requires further elucidation.

Purpose of the Study:

  • To investigate the role of PIK3R3 in regulating cellular senescence in colorectal cancer.
  • To elucidate the molecular mechanism by which PIK3R3 influences the p53/p21 signaling pathway.
  • To assess the potential of targeting PIK3R3 as a therapeutic strategy for colorectal cancer.

Main Methods:

  • Investigated the effect of PIK3R3 on colorectal cancer cell senescence and proliferation.
  • Utilized molecular biology techniques to examine the interaction between PIK3R3 and p53.
  • Analyzed the impact of PIK3R3 on the binding of p53 to the p21 gene promoter.

Main Results:

  • PIK3R3 was found to inhibit cellular senescence in colorectal cancer cells, promoting their proliferation.
  • PIK3R3 directly binds to p53, hindering its association with the p21 gene promoter region.
  • This interaction consequently affects the transcriptional activity of the p21 gene, a key regulator of senescence.

Conclusions:

  • PIK3R3 plays a significant role in regulating p53 activity and inhibiting cellular senescence in colorectal cancer.
  • Targeting PIK3R3 presents a potential novel therapeutic approach for colorectal cancer treatment.
  • Further research into PIK3R3 inhibition could lead to effective anti-cancer therapies.

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...
5.0K
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.
37.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.4K
DNA Damage can Stall the Cell Cycle02:37

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...
9.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.9K