Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

7.2K
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...
7.2K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

17.0K
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...
17.0K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

10.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

11.8K
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...
11.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

5.3K
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...
5.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

4.6K
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...
4.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Glutamate Ionotropic Kainate Receptors as Therapeutic Targets in Enzalutamide-Resistant and Neuroendocrine Prostate Cancer.

International journal of molecular sciences·2026
Same author

A Narrative Review of Stem Cell-Derived Exosomes for Diabetic Nephropathy.

Stem cells international·2026
Same author

A Phase I trial of PLZ4-coated paclitaxel-loaded micelles in patients with refractory non-muscle-invasive bladder cancer.

Nanomedicine (London, England)·2026
Same author

Multicenter, Randomized, Phase II Trial of Olaparib Plus Radium-223 Versus Radium-223 in Men With Castration-Resistant Prostate Cancer With Bone Metastases (COMRADE).

Journal of clinical oncology : official journal of the American Society of Clinical Oncology·2026
Same author

Targeting NDUFS4 Disrupts Oxidative Phosphorylation and Induces Ferroptosis in Olaparib-Resistant Prostate Cancer.

Molecular cancer therapeutics·2026
Same author

Targeting NDUFS4 Disrupts Oxidative Phosphorylation and Induces Ferroptosis in Olaparib-Resistant Prostate Cancer.

Molecular cancer therapeutics·2026

Related Experiment Video

Updated: Jan 9, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.2K

IGFBP3-SphK1/S1P Signaling Axis Drives Enzalutamide Resistance in Advanced Prostate Cancer.

Amy R Leslie1, Shu Ning1, Masuda Sharifi1

  • 1Department of Urologic Surgery, University of California Davis, Sacramento, California.

Molecular Cancer Therapeutics
|December 5, 2025
PubMed
Summary

Insulin-like growth factor binding protein 3 (IGFBP3) drives enzalutamide resistance in advanced prostate cancer by activating the SphK1/S1P pathway. Targeting this axis offers a new strategy to overcome treatment resistance.

More Related Videos

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

13.7K
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

35.8K

Related Experiment Videos

Last Updated: Jan 9, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.2K
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

13.7K
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

35.8K

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Enzalutamide resistance is a major obstacle in advanced prostate cancer treatment.
  • Identifying molecular mechanisms of resistance is critical for therapeutic development.

Purpose of the Study:

  • To identify key molecular drivers of enzalutamide resistance in castration-resistant prostate cancer (CRPC).
  • To investigate the role of insulin-like growth factor binding protein 3 (IGFBP3) in mediating enzalutamide resistance.
  • To explore the therapeutic potential of targeting the IGFBP3 signaling pathway.

Main Methods:

  • Analysis of IGFBP3 expression in enzalutamide-resistant CRPC cell lines and patient samples.
  • Investigated the effect of IGFBP3 modulation (knockdown/overexpression) on enzalutamide sensitivity.
  • Examined the activation of the sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) pathway.
  • Utilized siRNA for IGFBP3 inhibition and SKI-II as a SphK1 inhibitor in preclinical models.

Main Results:

  • IGFBP3 expression is significantly upregulated in enzalutamide-resistant CRPC cells and patient samples, correlating with poor survival.
  • Enzalutamide treatment directly induces IGFBP3 expression.
  • IGFBP3 activates the SphK1/S1P pathway, promoting cell survival and resistance.
  • IGFBP3 knockdown or SphK1 inhibition re-sensitized resistant cells to enzalutamide and reduced tumor growth.

Conclusions:

  • IGFBP3 is a critical mediator of enzalutamide resistance in advanced prostate cancer.
  • The IGFBP3-SphK1-S1P signaling axis represents a novel therapeutic target.
  • Targeting this axis holds promise for overcoming enzalutamide resistance in CRPC patients.