Related Experiment Video

Updated: Apr 16, 2026

A Cancer Cell Spheroid Assay to Assess Invasion in a 3D Setting
05:34

A Cancer Cell Spheroid Assay to Assess Invasion in a 3D Setting

Published on: November 20, 2015

34.5K

Androgen receptor non-nuclear regulation of prostate cancer cell invasion mediated by Src and matriptase

Jelani C Zarif1,2, Laura E Lamb3, Veronique V Schulz1

  • 1Laboratory of Integrin Signaling and Tumorigenesis, Van Andel Research Institute, Grand Rapids, MI 49503, USA.

Oncotarget
|March 3, 2015
PubMed

Insights

Androgen signaling in prostate cancer cells rapidly activates cytoplasmic androgen receptor (AR), stimulating Src kinase. This non-genomic pathway promotes tumor invasion via Matriptase activation, even in resistant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Castration-resistant prostate cancer (CRPC) remains dependent on androgen receptor (AR) signaling.
  • While nuclear AR is targeted by therapies, resistance develops, often associated with elevated Src activity.
  • The non-genomic roles of cytoplasmic AR in CRPC progression are not fully understood.

Purpose of the Study:

  • To investigate the non-genomic mechanism by which cytoplasmic androgen receptor (AR) influences Src activity and prostate cancer invasion.
  • To elucidate the role of the cytoplasmic AR-Src pathway in activating downstream effectors like Matriptase and CDCP1/gp140.
  • To determine the therapeutic potential of targeting this pathway in prostate cancer.

Main Methods:

  • Utilized RNA interference (RNAi), drug treatments, and a nuclear-deficient AR mutant to manipulate AR activity in prostate cancer cell lines.
  • Assessed Src tyrosine kinase activity and its downstream signaling pathways.
  • Measured invasion assays and analyzed the activation and shedding of Matriptase and CDCP1/gp140.

Main Results:

  • Androgen stimulation of cytoplasmic AR rapidly activates Src tyrosine kinase through a non-genomic mechanism.
  • The activated cytoplasmic AR-Src pathway enhances laminin integrin-dependent invasion.
  • Src-dependent activation and shedding of Matriptase, a laminin protease, are critical for promoting invasion, while CDCP1/gp140 activation is not sufficient to suppress invasion.

Conclusions:

  • Cytoplasmic AR initiates a rapid, non-genomic signaling cascade involving Src activation, leading to Matriptase-mediated prostate cancer cell invasion.
  • This pathway represents a potential therapeutic target for overcoming resistance in advanced prostate cancers.
  • Targeting Matriptase, rather than its substrate CDCP1, may be a more effective strategy to inhibit AR/Src-dependent invasion.
Keywords:
Srccastration-resistantmetastasisnongenomic AR signalingprostate cancer

More Related Videos

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

14.6K
An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

36.2K

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...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.8K
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...
8.5K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.5K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.5K