Related Experiment Video

Updated: Oct 12, 2025

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs
10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

11.1K

ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation

Yan Gu1, Yanrong Chen1, Lai Wei1

  • 1Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China.

Nature Communications
|November 19, 2021
PubMed

Insights

Loss of ABHD5 promotes colorectal cancer (CRC) stemness by enabling c-Met activation. This occurs through DPY30 nuclear translocation, leading to YAP methylation and increased c-Met transcription, highlighting a new regulatory pathway in CRC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer stemness drives colorectal cancer (CRC) development and progression.
  • c-Met signaling is crucial for CRC stemness, but its activation mechanism is unclear.
  • ABHD5, a lipolytic factor, acts as a tumor suppressor in CRC.

Purpose of the Study:

  • To elucidate the mechanism by which ABHD5 loss promotes c-Met activation and sustains CRC stemness.
  • To investigate the role of ABHD5 in regulating DPY30, SET1A, and YAP interactions in CRC cells.

Main Methods:

  • Investigated the interaction between ABHD5 and DPY30 in the cytoplasm.
  • Assessed the effect of ABHD5 on DPY30 nuclear translocation and SET1A methyltransferase activity.
  • Analyzed SET1A-mediated methylation of YAP and histone H3.
  • Examined the impact on YAP nuclear sequestration and c-Met transcription.

Main Results:

  • Loss of ABHD5 facilitates the nuclear translocation of DPY30, a subunit of the SET1A complex.
  • Nuclear DPY30 enhances SET1A activity, leading to YAP and histone H3 methylation.
  • This methylation process increases YAP nuclear retention and chromatin accessibility.
  • Consequently, YAP-induced c-Met transcription is upregulated, promoting CRC stemness.

Conclusions:

  • ABHD5 loss promotes CRC stemness via a non-canonical pathway involving DPY30 and SET1A.
  • ABHD5 regulates histone and non-histone methylation, impacting YAP activity and c-Met expression.
  • This finding reveals a novel regulatory mechanism controlling CRC stemness and offers potential therapeutic targets.

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

7.1K
All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System09:55

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System

Published on: December 20, 2021

3.1K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.0K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.5K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.2K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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...
7.9K