Related Experiment Video
Updated: Apr 6, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
LMTK3 Represses Tumor Suppressor-like Genes through Chromatin Remodeling in Breast Cancer
Yichen Xu1, Hua Zhang1, Van Thuy Mai Nguyen1
1Division of Cancer, Imperial College London, Department of Surgery and Cancer, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Abstract:
LMTK3 is an oncogenic receptor tyrosine kinase (RTK) implicated in various types of cancer, including breast, lung, gastric, and colorectal cancer. It is localized in different cellular compartments, but its nuclear function has not been investigated so far. We mapped LMTK3 binding across the genome using ChIP-seq and found that LMTK3 binding events are correlated with repressive chromatin markers. We further identified KRAB-associated protein 1 (KAP1) as a binding partner of LMTK3. The LMTK3/KAP1 interaction is stabilized by PP1α, which suppresses KAP1 phosphorylation specifically at LMTK3-associated chromatin regions, inducing chromatin condensation and resulting in transcriptional repression of LMTK3-bound tumor suppressor-like genes. Furthermore, LMTK3 functions at distal regions in tethering the chromatin to the nuclear periphery, resulting in H3K9me3 modification and gene silencing. In summary, we propose a model where a scaffolding function of nuclear LMTK3 promotes cancer progression through chromatin remodeling.
Insights
Nuclear LMTK3 (Lemur tyrosine kinase 3) acts as a scaffold to remodel chromatin, promoting cancer progression. This involves gene silencing and chromatin condensation, impacting tumor suppressor-like genes.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Lemur tyrosine kinase 3 (LMTK3) is an oncogenic receptor tyrosine kinase (RTK) involved in multiple cancers.
- The nuclear functions and chromatin interactions of LMTK3 remain largely uncharacterized.
Purpose of the Study:
- To investigate the nuclear role of LMTK3 in chromatin regulation.
- To elucidate the molecular mechanisms by which LMTK3 influences gene expression in cancer.
Main Methods:
- Genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) to map LMTK3 binding sites.
- Identification of LMTK3 interacting proteins, including KAP1.
- Analysis of chromatin markers and gene expression changes associated with LMTK3 activity.
Main Results:
- LMTK3 binds to genomic regions associated with repressive chromatin markers.
- LMTK3 interacts with KRAB-associated protein 1 (KAP1), stabilized by PP1α, leading to KAP1 dephosphorylation and chromatin condensation.
- Nuclear LMTK3 recruits chromatin to the nuclear periphery, promoting H3K9me3 modification and silencing of tumor suppressor-like genes.
Conclusions:
- Nuclear LMTK3 functions as a scaffold protein that induces chromatin remodeling and gene silencing.
- This mechanism contributes to cancer progression by repressing tumor suppressor-like genes.
- LMTK3's role in chromatin organization offers potential therapeutic targets for cancer treatment.
More Related Videos
05:58Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells
Published on: February 24, 2026
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Related Concept Videos
02:23Abnormal Proliferation
02:39lncRNA - Long Non-coding RNAs
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes