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

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
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

12.2K
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...
12.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

8.6K
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...
8.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

5.4K
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...
5.4K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

17.5K
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...
17.5K
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

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

Commensurate prior models with random effects for interval-censored data to accommodate historical controls.

Communications in statistics: Simulation and computation·2026
Same author

Differential Myelin and Axon-Dependent Recovery Based on Symptom Duration in Degenerative Cervical Myelopathy.

Neurosurgery·2026
Same author

Machine learning-based MRI radiomics identifies patients with degenerative cervical myelopathy and predicts baseline function.

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·2026
Same author

Prostate Cancer Biomarkers with a Focus on Galectin-3: Emerging Clinical and Therapeutic Implications.

Current oncology (Toronto, Ont.)·2026
Same author

How does AI perform compared to human expert panels in medical Delphi studies? A pilot study through the lens of pathology.

Journal of pathology informatics·2026

Related Experiment Video

Updated: Jan 19, 2026

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

Enzalutamide-Induced Feed-Forward Signaling Loop Promotes Therapy-Resistant Prostate Cancer Growth Providing an

Vindhya Udhane1,2,3, Cristina Maranto1,2,3, David T Hoang4

  • 1Department of Pathology, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin.

Molecular Cancer Therapeutics
|September 25, 2019
PubMed
Summary

Enzalutamide resistance in prostate cancer involves Jak2-Stat5 signaling. Inhibiting this pathway can overcome resistance and block tumor growth, offering a new therapeutic strategy for advanced prostate cancer.

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.2K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

641

Related Experiment Videos

Last Updated: Jan 19, 2026

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
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.2K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

641

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Enzalutamide is a second-generation antiandrogen used for castrate-resistant prostate cancer (CRPC).
  • Acquired resistance to enzalutamide is a significant clinical challenge, leading to disease progression.
  • Signal transducer and activator of transcription 5 (Stat5) is known to promote prostate cancer growth.

Purpose of the Study:

  • To investigate the role of Janus kinase 2 (Jak2)-Stat5 signaling in enzalutamide resistance in prostate cancer.
  • To evaluate Jak2-Stat5 signaling as a therapeutic target for overcoming enzalutamide resistance.

Main Methods:

  • Assessed Jak2 and Stat5 levels and activation in prostate cancer cells, xenografts, and patient samples before and after enzalutamide treatment.
  • Utilized genetic knockdown (shRNA) and pharmacologic inhibitors to suppress Jak2-Stat5 signaling.
  • Evaluated in vivo tumor growth and ex vivo patient-derived cancer responsiveness to Jak2-Stat5 inhibition.

Main Results:

  • Enzalutamide treatment induced sustained Jak2-Stat5 phosphorylation, forming a positive feedback loop that enhances Jak2 activity.
  • Activated Stat5 promoted prostate cancer growth during enzalutamide treatment.
  • Inhibition of Jak2-Stat5 signaling led to prostate cancer cell death, overcame enzalutamide resistance in patient-derived cancers, and blocked resistant tumor growth in mice.

Conclusions:

  • Hyperactivated Jak2-Stat5 signaling plays a pivotal role in enzalutamide-resistant prostate cancer.
  • Targeting Jak2-Stat5 signaling represents a novel and effective strategy for treating enzalutamide-resistant prostate cancer.
  • Jak2 inhibitors in clinical development show promise for overcoming enzalutamide resistance.