Related Experiment Video

Updated: Jan 14, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.4K

Disrupting Paraspeckle Stability by Targeting WTX-NONO Phase Separation Enhances Chemotherapy Efficacy in Gastric

Yangwei Xu1,2, Zaisheng Ye3, Zhihao Lin1,2

  • 1Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

Cancer Research
|October 20, 2025
PubMed

Insights

The short WTX isoform (WTX-S) disrupts nuclear paraspeckles by sequestering NONO, enhancing gastric cancer chemotherapy sensitivity. A synthetic peptide, WTXAP, shows antitumor activity by mimicking this effect.

Area of Science:

  • Nuclear biology
  • Cancer research
  • Molecular oncology

Background:

  • Nuclear paraspeckles are crucial for gene transcription in tumor development.
  • Identifying regulators of paraspeckle dynamics is key for cancer therapy targets.

Purpose of the Study:

  • To investigate the role of the WTX protein, specifically its short isoform (WTX-S), in regulating paraspeckle stability.
  • To explore the therapeutic potential of targeting paraspeckle disruption in gastric cancer.

Main Methods:

  • Investigated WTX-S interaction with NONO (p54nrb) and its effect on paraspeckles.
  • Characterized the formation of WTX-induced nuclear bodies (WTX-NBs) via liquid-liquid phase separation.
  • Assessed the impact of paraspeckle disintegration on gastric cancer (GC) chemotherapy sensitivity and prognosis.
  • Evaluated the antitumor activity of the synthetic peptide WTXAP and XPO1 inhibitor KPT-330.

Main Results:

  • WTX-S selectively sequesters NONO, disrupting paraspeckle stability through WTX-NB formation.
  • WTX-NB-induced paraspeckle disintegration enhances chemotherapy sensitivity and improves prognosis in GC.
  • The synthetic peptide WTXAP mimics WTX-NB effects and demonstrates potent antitumor activity.
  • KPT-330 enhances WTX-S-mediated paraspeckle disruption, sensitizing GC to chemotherapy.

Conclusions:

  • WTX-NBs represent a novel mechanism for paraspeckle regulation with significant clinical implications.
  • Targeting WTX-NB formation offers a promising strategy to sensitize gastric cancer to chemotherapy.
  • WTXAP peptide and KPT-330 show potential as therapeutic agents for gastric cancer treatment.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.8K
Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.6K

Related Concept Videos

Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
3.6K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.6K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
574
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K