Related Experiment Video

Updated: Oct 27, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

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

Published on: March 6, 2018

13.4K

SHH-N non-canonically sustains androgen receptor activity in androgen-independent prostate cancer cells

Diana Trnski1, Maja Sabol2, Sanja Tomić3

  • 1Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, 10000, Zagreb, Croatia. Diana.Trnski@irb.hr.

Scientific Reports
|July 22, 2021
PubMed

Insights

Hedgehog-GLI signaling sustains advanced prostate cancer growth by activating the androgen receptor. Targeting the SHH-N ligand

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Prostate cancer is a leading global cancer in men.
  • Advanced prostate cancer often becomes resistant to androgen deprivation therapy (ADT).
  • Hedgehog-GLI (HH-GLI) signaling is implicated in various cancers.

Purpose of the Study:

  • Investigate the role of HH-GLI signaling in androgen-independent prostate cancer growth.
  • Elucidate the mechanisms of HH-GLI pathway activation in prostate cancer cells under different androgen conditions.
  • Identify potential therapeutic targets for advanced prostate cancer.

Main Methods:

  • Analysis of HH-GLI signaling activation in prostate cancer cells with varying androgen levels.
  • Investigation of non-canonical SMO signaling via SRC kinase.
  • Examination of canonical HH-GLI signaling post-androgen deprivation.
  • Assessment of SHH-N ligand interaction with the androgen receptor (AR) in androgen-independent cells.

Main Results:

  • HH-GLI signaling activation varies with androgen availability.
  • Non-canonical SMO signaling observed with SRC kinase when androgens are present.
  • Canonical HH-GLI signaling activated after short-term androgen deprivation.
  • SHH-N ligand non-canonically binds to AR via cholesterol modification in androgen-independent cells.
  • Inhibition of SHH-N/AR interaction downregulates AR signaling.

Conclusions:

  • SHH-N activates the androgen receptor, sustaining androgen-independent prostate cancer growth.
  • Targeting the SHH-N/AR interaction is a potential therapeutic strategy for advanced prostate cancer.
  • Further investigation of non-canonical HH-GLI signaling aspects is warranted for therapy development.

More Related Videos

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses08:36

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses

Published on: October 24, 2019

11.4K
An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

35.4K

Related Concept Videos

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...
4.0K
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...
4.8K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.9K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.7K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.6K
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...
7.2K