Related Experiment Video

Updated: Mar 9, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

6.9K

KLF4 functions as an activator of the androgen receptor through reciprocal feedback

M-K Siu1,2,3, F Suau4, W-Y Chen5,6

  • 1Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.

Oncogenesis
|December 20, 2016
PubMed

Insights

Loss of Krüppel-like factor 4 (KLF4) in prostate cancer is linked to reduced androgen receptor (AR) and microRNA-1 (miR-1). Restoring KLF4 suppresses tumor progression and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Krüppel-like factor 4 (KLF4) is frequently depleted in prostate cancer, indicating a tumor suppressor role.
  • KLF4's association with androgen receptor (AR) expression is known, but its regulatory mechanisms and functions are unclear.

Purpose of the Study:

  • To elucidate the regulatory relationship between KLF4 and AR in prostate cancer.
  • To investigate the role of KLF4 in regulating microRNA-1 (miR-1) expression and its impact on prostate cancer progression.

Main Methods:

  • Investigated AR binding to the KLF4 promoter and KLF4's effect on the AR promoter.
  • Assessed the impact of ectopic KLF4 expression on androgen-independent prostate cancer cell proliferation, invasion, and bone metastasis.
  • Examined KLF4's regulation of the miR-1-2 promoter and correlated KLF4, miR-1, and AR levels in clinical specimens.

Main Results:

  • Activated AR enhances KLF4 expression, which reciprocally targets the AR promoter, creating a positive feedback loop.
  • Ectopic KLF4 expression in androgen-independent cells increased AR, suppressed proliferation, invasion, and bone metastasis.
  • KLF4 was found to stimulate miR-1 expression by targeting its promoter. KLF4, miR-1, and AR levels were positively correlated in clinical prostate cancer samples.

Conclusions:

  • KLF4 plays a crucial role in maintaining AR signaling and suppressing prostate cancer progression.
  • Loss of KLF4 contributes to aggressive prostate cancer by inactivating the miR-1 pathway and reducing AR output.
  • KLF4 represents a potential therapeutic target for prostate cancer treatment.

More Related Videos

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

13.2K
A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

9.6K

Related Concept Videos

Testosterone: Functions and Regulation01:26

Testosterone: Functions and Regulation

The intricate hormonal interplay essential for male reproductive health begins with the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus. This hormone prompts the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). LH targets the Leydig cells in the testes, stimulating them to produce and release testosterone. In concert with testosterone, FSH acts on the Sertoli cells within the seminiferous tubules to facilitate the release of...
2.7K
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
12.2K
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
75.7K
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...
7.6K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.0K
Intracellular Hormone Receptors01:08

Intracellular Hormone Receptors

Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
61.8K