Related Experiment Video

Updated: Oct 15, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

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

7.3K

JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12

Yan Liang1, Chao Qian2, Yinghong Xie1

  • 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Cell Death Discovery
|October 23, 2021
PubMed

Insights

JWA (Junctional Interacting Protein) is downregulated in trastuzumab-resistant breast cancer, hindering tumor suppression. Restoring JWA levels may offer a new therapeutic strategy for improving patient survival rates.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer is a global health concern, with trastuzumab resistance posing a significant clinical challenge.
  • JWA (Junctional Interacting Protein) functions as a tumor suppressor, and its reduced expression correlates with poor prognosis in various cancers.
  • Understanding JWA's role in trastuzumab resistance is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the expression, regulation, and functional mechanism of JWA in trastuzumab-resistant breast cancer.
  • To evaluate JWA as a potential predictive marker and therapeutic target for trastuzumab-resistant breast cancer.

Main Methods:

  • Comparative analysis of JWA expression in trastuzumab-resistant versus sensitive breast cancer models.
  • In vitro and in vivo experiments to assess the effects of JWA overexpression on cancer cell proliferation and apoptosis.
  • Integration of RNA-sequencing and next-generation sequencing data to elucidate JWA's regulatory pathways.
  • Correlation analysis between JWA expression levels and patient prognosis.

Main Results:

  • JWA expression was significantly lower in trastuzumab-resistant breast cancers compared to sensitive ones.
  • Overexpression of JWA inhibited proliferation and promoted apoptosis in trastuzumab-resistant breast cancer cells, both in vitro and in vivo.
  • Low JWA expression was associated with a poor prognosis in patients with trastuzumab-resistant breast cancer.
  • JWA was found to negatively regulate CDK12, a gene implicated in cell cycle progression and trastuzumab resistance.

Conclusions:

  • JWA expression is reduced in trastuzumab-resistant breast cancer and its restoration can inhibit tumor growth.
  • JWA serves as a potential predictive biomarker for trastuzumab resistance.
  • Targeted JWA therapy presents a promising novel strategy to improve outcomes for patients with trastuzumab-resistant breast cancer.

More Related Videos

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

18.8K
High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds13:59

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds

Published on: August 18, 2023

2.3K

Related Concept Videos

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...
5.0K
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...
4.7K
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...
7.9K
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...
3.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.4K
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...
6.6K