Related Experiment Video

Updated: Aug 30, 2025

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

233

ABL kinases regulate translation in HER2+ cells through Y-box-binding protein 1 to facilitate colonization of the

Courtney M McKernan1, Aaditya Khatri2, Molly Hannigan3

  • 1Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.

Cell Reports
|August 31, 2022
PubMed

Insights

Abelson kinase inhibitors improve survival and reduce brain metastasis in HER2-positive breast cancer by decreasing HER2 protein. This targets the Y-box-binding protein 1 (YB-1) pathway, offering new hope for patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Neuroscience

Background:

  • HER2-positive breast cancer frequently metastasizes to the brain.
  • Existing HER2-targeted therapies show limited efficacy against brain metastases due to poor blood-brain barrier penetration and resistance.
  • Novel therapeutic strategies are needed to effectively treat HER2+ brain metastases.

Purpose of the Study:

  • To investigate the efficacy of Abelson (ABL) kinase inhibitors in treating HER2+ brain metastases.
  • To elucidate the molecular mechanisms by which ABL kinase inhibition affects HER2 expression and brain metastatic outgrowth.

Main Methods:

  • In vivo studies using mouse models of HER2+ brain metastasis.
  • Assessment of overall survival and metastatic outgrowth.
  • Analysis of ABL kinase activity, Y-box-binding protein 1 (YB-1) phosphorylation, and ERBB2 mRNA translation.

Main Results:

  • ABL kinase allosteric inhibitors significantly improved overall survival and reduced HER2+ brain metastatic outgrowth in vivo.
  • ABL kinase inhibition disrupted the binding of YB-1 to ERBB2 mRNA, impairing HER2 translation and reducing HER2 protein levels.
  • Loss of YB-1 also inhibited brain metastatic outgrowth and affected ABL-dependent metastatic targets.

Conclusions:

  • ABL kinases play a crucial role in the translational regulation of HER2 and other brain metastatic targets via YB-1.
  • ABL kinase inhibition represents a promising therapeutic strategy for patients with HER2+ breast cancer brain metastases.
  • Targeting the ABL-YB-1-HER2 axis offers a novel approach to overcome treatment resistance in brain metastases.
Keywords:
ABL kinaseCP: CancerCP: Molecular biologyHER2RNA-binding proteinY-box-binding protein 1brain metastasisbreast cancermRNA translation

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.0K
Real-Time Quantitative Measurement of Tumor Cell Migration and Invasion Following Synthetic mRNA Transfection11:00

Real-Time Quantitative Measurement of Tumor Cell Migration and Invasion Following Synthetic mRNA Transfection

Published on: June 23, 2023

1.2K

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...
3.9K
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...
3.9K
Regulated mRNA Transport02:22

Regulated mRNA Transport

In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
79.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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...
6.4K
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...
6.6K