Related Experiment Video

Updated: Nov 15, 2025

The Soft Agar Colony Formation Assay
08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

112.9K

Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer

Shannon E Weeks1, Sarah C Kammerud1, Brandon J Metge1

  • 1Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.

Cell Death & Disease
|March 5, 2021
PubMed

Insights

Triple-negative breast cancer (TNBC) cells exhibit increased nucleoli, linked to Wnt/β-catenin signaling. This pathway regulates LAS1L, a protein crucial for TNBC growth and invasion, revealing a novel therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis.
  • Upregulated Wnt/β-catenin signaling is common in TNBC and associated with adverse outcomes.
  • An increased number of nucleoli was observed in TNBC tissues compared to non-TNBC.

Purpose of the Study:

  • To investigate the functional role of the nucleolus in TNBC.
  • To determine the relationship between Wnt/β-catenin signaling and nucleolar activity in TNBC.
  • To identify key nucleolar proteins regulated by β-catenin in TNBC.

Main Methods:

  • Comparative nucleolar proteomics of TNBC and non-TNBC cells.
  • Analysis of nucleolar proteome changes following β-catenin inhibition in TNBC cells.
  • Assessment of LAS1L protein expression in TNBC patient tissues and xenograft models.

Main Results:

  • TNBC cells show a higher abundance of nucleoli, directly correlating with nuclear β-catenin levels.
  • Proteomic analysis revealed that most nucleolar proteins in TNBC cells are potential β-catenin targets.
  • LAS1-like ribosome biogenesis factor (LAS1L) was identified as a key nucleolar protein downregulated upon β-catenin inhibition.
  • LAS1L is significantly elevated in TNBC patients and promotes tumor growth and invasion in vivo.

Conclusions:

  • Wnt/β-catenin signaling plays a novel role in regulating nucleolar activity in TNBC.
  • LAS1L is a critical mediator of β-catenin's effects on nucleolar function and TNBC progression.
  • Targeting the β-catenin-nucleolus-LAS1L axis may offer a new therapeutic strategy for TNBC.

More Related Videos

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

18.5K
Reconstitution Of β-catenin Degradation In Xenopus Egg Extract09:41

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract

Published on: June 17, 2014

12.3K

Related Concept Videos

Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.7K
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...
5.3K
The Nucleolus02:55

The Nucleolus

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
9.8K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
9.5K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.9K
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.
37.4K