Related Experiment Video

Updated: Feb 16, 2026

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
06:02

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers

Published on: February 20, 2017

8.0K

FOXJ1 mediates taxane resistance through regulation of microtubule dynamics

Fang Xie1, Ada Gjyrezi2, Daniel Fein1

  • 1Department of Medicine, Division of Oncology and Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Nature Communications
|February 14, 2026
PubMed

Insights

FOXJ1 gene expression drives docetaxel resistance in prostate cancer (PC) by altering microtubule dynamics. Targeting this FOXJ1 pathway may help identify patients unlikely to benefit from taxane chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Docetaxel is a primary chemotherapy for metastatic prostate cancer (PC).
  • Mechanisms underlying docetaxel resistance in PC are not fully understood.
  • Understanding resistance mechanisms is crucial for improving treatment efficacy.

Purpose of the Study:

  • To investigate the role of FOXJ1 and its associated signaling in docetaxel resistance in prostate cancer.
  • To establish the mechanistic link between FOXJ1, microtubule biology, and taxane resistance.
  • To explore the clinical relevance of FOXJ1 as a predictive biomarker for taxane treatment.

Main Methods:

  • Utilized in vivo models of docetaxel-resistant PC patient-derived xenografts.
  • Assessed gene expression changes, focusing on FOXJ1 and its downstream effectors.
  • Performed in vitro and in vivo experiments to evaluate the functional impact of FOXJ1 modulation on docetaxel sensitivity.
  • Analyzed clinical data from the CHAARTED trial and patient samples for FOXJ1 amplification and expression.

Main Results:

  • Increased expression of FOXJ1 and its effectors, which regulate microtubules (MTs), was observed in docetaxel-resistant PC xenografts.
  • FOXJ1 overexpression conferred docetaxel resistance by decreasing docetaxel-mediated MT bundling.
  • Knockdown of FOXJ1 enhanced docetaxel sensitivity by improving MT function and taxane binding.
  • FOXJ1 gene amplification was elevated in taxane-treated PC patients, and high baseline FOXJ1 predicted poorer survival in the CHAARTED trial.

Conclusions:

  • The FOXJ1 signaling axis is mechanistically linked to microtubule biology and confers taxane resistance in prostate cancer.
  • FOXJ1 represents a novel, clinically relevant mechanism of docetaxel resistance.
  • Exploiting the FOXJ1 pathway could enable patient stratification for taxane-based therapies.

More Related Videos

Measurement of Microtubule Dynamics by Spinning Disk Microscopy in Monopolar Mitotic Spindles08:31

Measurement of Microtubule Dynamics by Spinning Disk Microscopy in Monopolar Mitotic Spindles

Published on: November 15, 2019

6.7K
Simultaneous Visualization of the Dynamics of Crosslinked and Single Microtubules In Vitro by TIRF Microscopy07:20

Simultaneous Visualization of the Dynamics of Crosslinked and Single Microtubules In Vitro by TIRF Microscopy

Published on: February 18, 2022

3.1K

Related Concept Videos

Microtubules01:35

Microtubules

There are three types of cytoskeletal structures in eukaryotic cells—microfilaments, intermediate filaments, and microtubules. With a diameter of about 25 nm, microtubules are the thickest of these fibers. Microtubules carry out a variety of functions that include cell structure and support, transport of organelles, cell motility (movement), and the separation of chromosomes during cell division.
101.6K
Microtubules01:18

Microtubules

Microtubules are the thickest cytoskeletal filaments with a diameter of 25 nm. In prokaryotic organisms, microtubules are commonly found in locomotory appendages like cilia and flagella. In eukaryotic cells, microtubules form specialized extensions for moving fluid over the surface, like those found in cells lining the intestine.
Microtubules have two structurally similar globular protein subunits: α and β tubulins. In the cytosol, the α and β tubulins form a heterodimer....
10.9K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
6.3K
Microtubule Formation01:23

Microtubule Formation

Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation...
7.8K
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
3.7K