Related Experiment Video

Updated: Jul 9, 2025

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

2.7K

Deubiquitinating enzyme OTUD4 regulates metastasis in triple-negative breast cancer by stabilizing Snail1

Xiuqing Ma1, Rui Wan1, Yalei Wen2

  • 1College of Pharmacy/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou, China.

Experimental Cell Research
|December 1, 2023
PubMed

Insights

Deubiquitinase OTU domain containing 4 (OTUD4) promotes triple-negative breast cancer (TNBC) metastasis by stabilizing Snail1. Targeting OTUD4 may offer new therapeutic strategies for TNBC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis Research

Background:

  • Metastasis is the leading cause of cancer mortality, yet its mechanisms are not fully understood.
  • Deubiquitinase OTU domain containing 4 (OTUD4) is implicated in immune responses and therapy resistance, but its role in cancer spread is unknown.

Purpose of the Study:

  • To investigate the role of OTUD4 in the metastasis of triple-negative breast cancer (TNBC).
  • To elucidate the molecular mechanisms by which OTUD4 influences TNBC metastasis.

Main Methods:

  • Depletion of OTUD4 in TNBC cells.
  • In vitro assays assessing cell clonogenicity, migration, invasion, and cancer stem cell populations.
  • In vivo metastasis assays.
  • Mechanistic studies involving Snail1 ubiquitination and stabilization.

Main Results:

  • OTUD4 depletion significantly suppressed TNBC cell proliferation, migration, invasion, and stemness in vitro, and reduced metastasis in vivo.
  • OTUD4 promotes metastasis by deubiquitinating and stabilizing the key epithelial-mesenchymal transition transcription factor, Snail1.
  • Reintroducing Snail1 reversed the inhibitory effects of OTUD4 deficiency.

Conclusions:

  • The OTUD4-Snail1 axis is a critical regulator of breast cancer metastasis, particularly in TNBC.
  • Targeting OTUD4 presents a potential therapeutic strategy for inhibiting TNBC metastasis.
Keywords:
DeubiquitinationMetastasisOTUD4Snail1Triple-negative breast cancer

More Related Videos

The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior08:12

The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior

Published on: June 12, 2019

5.2K
Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

10.9K

Related Concept Videos

Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.6K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.1K
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...
3.8K
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...
4.5K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.7K