Related Experiment Video

Updated: Dec 24, 2025

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
19:44

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

19.1K

Golgi-Localized PAQR4 Mediates Antiapoptotic Ceramidase Activity in Breast Cancer

Line Pedersen1, Pouda Panahandeh1, Muntequa I Siraji1

  • 1Department of Biomedicine, University of Bergen, Bergen, Norway.

Cancer Research
|April 16, 2020
PubMed

Insights

Progestin and adipoQ receptor family member IV (PAQR4) acts as a Golgi-localized ceramidase crucial for breast cancer growth. Its upregulation in tumors indicates a potential therapeutic target for sphingolipid metabolism in cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Sphingolipids, including ceramides and sphingosine-1-phosphate, are critical regulators of cellular processes like growth and apoptosis.
  • While many enzymes in the sphingolipid pathway are known, several remain poorly understood, particularly in the context of cancer.

Purpose of the Study:

  • To identify and characterize novel enzymatic regulators of sphingolipid metabolism in breast cancer.
  • To investigate the role of progestin and adipoQ receptor family member IV (PAQR4) in breast cancer progression and its potential as a therapeutic target.

Main Methods:

  • Utilized a patient-derived systemic approach to identify PAQR4.
  • Performed molecular characterization of PAQR4, including its localization and enzymatic activity.
  • Analyzed PAQR4 expression levels in breast cancer tissues and correlated them with clinical outcomes.

Main Results:

  • Identified PAQR4 as a Golgi-localized ceramidase.
  • Found PAQR4 to be upregulated approximately 5-fold in breast cancer tissues compared to controls.
  • Demonstrated that PAQR4 overexpression correlates with poorer disease-specific survival rates in breast cancer patients.
  • Observed that PAQR4 induction is subtype-independent and linked to increased ceramidase activity.

Conclusions:

  • PAQR4 is a critical Golgi-localized ceramidase essential for cellular growth in breast cancer.
  • The induction of and cellular reliance on *de novo* sphingolipid synthesis via PAQR4 represent a significant vulnerability in breast cancer.
  • PAQR4 emerges as a potential therapeutic target for breast cancer treatment by modulating sphingolipid metabolism.

More Related Videos

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

10.2K
Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

9.5K

Related Concept Videos

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...
8.0K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
13.6K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
13.5K
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...
5.0K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
7.8K
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...
5.5K