Related Experiment Video

Updated: Dec 6, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.9K

Increased Expression of NPM1 Suppresses p27Kip1 Function in Cancer Cells

Tatsuya Kometani1, Takuya Arai1, Taku Chibazakura1

  • 1Department of Bioscience, Tokyo University of Agriculture 1-1-1, Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.

Cancers
|October 14, 2020
PubMed

Insights

Nucleophosmin isoform 1 (NPM1) qualitatively suppresses p27 function in cancer cells. NPM1 knockdown restored p27 function, inhibiting cancer growth in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • p27Kip1 is a key cyclin-dependent kinase inhibitor often downregulated in cancers, correlating with malignancy.
  • Qualitative suppression of p27 function, rather than just low expression, was observed in some cancer cells.

Purpose of the Study:

  • To identify factors responsible for the qualitative suppression of p27 function in cancer.
  • To investigate the role of nucleophosmin isoform 1 (NPM1) in p27 regulation and cancer progression.

Main Methods:

  • Proteomic screening to identify p27-interacting proteins.
  • Overexpression and knockdown studies in normal and cancer cells.
  • In vitro functional assays.
  • Mouse xenograft models to assess tumor growth.

Main Results:

  • Nucleophosmin isoform 1 (NPM1) was identified as a novel p27-interacting factor.
  • NPM1 is highly expressed in some cancer cells and suppresses p27 function when overexpressed in normal cells.
  • NPM1 knockdown in cancer cells restored p27 function in vitro.
  • Combined p27 overexpression and NPM1 knockdown significantly suppressed tumor growth in mouse xenograft models.

Conclusions:

  • Increased NPM1 expression qualitatively suppresses p27 function in cancer cells.
  • NPM1 represents a potential therapeutic target for enhancing p27 activity and inhibiting cancer growth.
Keywords:
CDK inhibitorcancer cellscell proliferationmouse xenograft modelnucleophosmin isoform 1p27Kip1protein–protein interaction

More Related Videos

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

9.5K
Live-imaging of Breast Epithelial Cell Migration After the Transient Depletion of TIP6008:13

Live-imaging of Breast Epithelial Cell Migration After the Transient Depletion of TIP60

Published on: December 7, 2017

7.1K

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
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
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
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.4K
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
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...
7.8K