Related Experiment Video

Updated: Jul 20, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

6.9K

Androgen Receptor Variants Confer Castration Resistance in Prostate Cancer by Counteracting Antiandrogen-Induced

Rui Sun1,2,3, Binyuan Yan3,4, Hao Li3

  • 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Cancer Research
|August 1, 2023
PubMed

Insights

Androgen receptor (AR) inhibition resistance in prostate cancer involves the SLC7A11 gene. Androgen receptor variants upregulate SLC7A11, promoting resistance to anti-cancer therapies like enzalutamide by inhibiting ferroptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Advanced prostate cancer treatment relies on androgen deprivation and antiandrogens, but resistance is common.
  • Understanding resistance mechanisms is crucial for improving patient outcomes in prostate cancer therapy.

Approach:

  • Investigated the effect of enzalutamide (ENZ) on prostate cancer cells, assessing glutathione production, lipid peroxidation, and ferroptosis.
  • Performed a meta-analysis of transcriptomic data to link the androgen-AR axis with lipid metabolism.
  • Examined the role of the cystine transporter gene SLC7A11 as a direct target of full-length AR (AR-FL) and AR variants (AR-Vs).

Key Points:

  • Enzalutamide treatment decreased glutathione, increased lipid peroxidation, and induced ferroptosis in prostate cancer cells.
  • AR-FL and AR-Vs directly regulate SLC7A11 transcription, impacting ferroptosis.
  • AR-V-mediated SLC7A11 upregulation confers resistance to enzalutamide-induced ferroptosis.

Conclusions:

  • Ferroptosis induction is an anticancer mechanism of antiandrogens.
  • SLC7A11 is a direct target gene of both AR-FL and AR-Vs.
  • AR-V-driven SLC7A11 expression is a key mechanism linking ferroptosis resistance to prostate cancer progression and castration resistance.

More Related Videos

Murine Prostate Micro-dissection and Surgical Castration08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

45.8K
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.1K

Related Concept Videos

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...
3.3K
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...
4.8K
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...
7.7K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers01:22

Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers

α-Adrenergic antagonists, known as α-blockers, exert their effects by inhibiting α-adrenoceptors, leading to specific physiological actions. α1-blockers and α2-blockers have distinct pharmacological actions and therapeutic applications.
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
888