Related Experiment Video

Updated: Jan 12, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.6K

NUSAP1 Recruits DAXX to Suppress HIF-Driven Triple-Negative Breast Cancer Progression

Yating Du1, Jingjing Wang1, Min Wang1

  • 1Collaborative Innovation Center of Cell Biology in Universities of Shandong, Center for Cell Structure and Function, College of Life Sciences, Modern Industry Institute of Biomedicine, Shandong Normal University, Jinan, 250014, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 3, 2025
PubMed

Insights

Nucleolar and spindle-associated protein 1 (NUSAP1) acts as a tumor suppressor in triple-negative breast cancer (TNBC). NUSAP1 inhibits cancer progression by attenuating HIF transcriptional activity, and a modified NUSAP1 domain shows therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Nucleolar and spindle-associated protein 1 (NUSAP1) plays a context-dependent role in cancer.
  • Emerging evidence suggests NUSAP1 may function as a tumor suppressor, but the mechanisms are unclear.
  • Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.

Purpose of the Study:

  • To investigate the role of NUSAP1 in TNBC progression.
  • To elucidate the molecular mechanisms by which NUSAP1 suppresses TNBC.
  • To explore the therapeutic potential of targeting the NUSAP1 pathway in TNBC.

Main Methods:

  • NUSAP1 depletion in TNBC cells in vitro and in vivo.
  • Co-immunoprecipitation to study protein interactions (NUSAP1, HIFα, DAXX, SETDB1).
  • Chromatin immunoprecipitation to assess H3K9me3 deposition.
  • Development and testing of an engineered NUSAP1 microtubule-associated domain (TS-MAD).

Main Results:

  • NUSAP1 depletion enhanced TNBC cell proliferation, migration, and invasion, and promoted tumor growth in vivo.
  • NUSAP1 bridges HIFα and DAXX, recruiting SETDB1 to deposit H3K9me3 on hypoxia response elements (HREs), thus suppressing HIF transcriptional activity.
  • An engineered NUSAP1 domain (TS-MAD) inhibited HIF transcriptional activity and HIF-driven TNBC progression.
  • NUSAP1 is a hypoxia-inducible factor (HIF)-repressed gene in TNBC, and its low expression correlates with poor clinical outcomes.

Conclusions:

  • NUSAP1 functions as a tumor suppressor in TNBC by attenuating HIF transcriptional activity.
  • A novel HIF-NUSAP1 double-negative feedback loop exists in TNBC.
  • The engineered TS-MAD domain represents a potential therapeutic strategy for HIF-driven cancers like TNBC.
Keywords:
DAXXHIFNUSAP1hypoxiatriple‐negative breast cancer

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.4K
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

18.8K

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...
5.1K
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...
8.2K
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...
4.6K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
9.8K