Related Experiment Video

Updated: Jan 3, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

14.3K

DAPK1 loss triggers tumor invasion in colorectal tumor cells

Sara Steinmann1,2,3, Philipp Kunze1,2, Chuanpit Hampel1,2

  • 1Experimental Tumor Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Universitaetsstrasse 22, 91054, Erlangen, Germany.

Cell Death & Disease
|November 28, 2019
PubMed

Insights

Loss of Death-associated protein kinase 1 (DAPK1) in colorectal cancer (CRC) enhances metastasis. DAPK1 acts as an anti-metastatic player, suggesting its potential as a predictive biomarker for CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis Research

Background:

  • Colorectal cancer (CRC) remains a leading cause of cancer mortality globally.
  • Metastasis to distant organs is a major challenge in CRC treatment.
  • Understanding metastasis mechanisms and identifying biomarkers are crucial for improved patient outcomes.

Purpose of the Study:

  • To investigate the role of Death-associated protein kinase 1 (DAPK1) in colorectal cancer aggressiveness.
  • To determine the impact of DAPK1 deficiency on CRC metastasis and invasion.
  • To identify potential DAPK1-associated signaling pathways in CRC progression.

Main Methods:

  • Generation of DAPK1-deficient HCT116 monoclonal cell lines using CRISPR/Cas9 technology.
  • In vitro characterization of knockout cell lines, including invasion assays using a 3D rat brain model.
  • In vivo assessment of tumor growth and metastasis in the chorioallantoic membrane (CAM) model.
  • Analysis of gene expression signatures and signaling pathways (DAPK1-ERK1 axis).

Main Results:

  • Loss of DAPK1 significantly altered growth patterns and enhanced tumor budding in vivo.
  • DAPK1-deficient cells exhibited increased dissemination into chicken embryo organs.
  • Enhanced invasion capacity was observed in 3D in vitro models.
  • A novel DAPK1-loss gene expression signature indicated extracellular matrix remodeling and a stroma-typical pattern.

Conclusions:

  • DAPK1 functions as an anti-metastatic factor in colorectal cancer.
  • The DAPK1-ERK1 signaling axis is implicated in CRC metastatic progression.
  • DAPK1 represents a potential predictive biomarker for colorectal cancer metastasis.

More Related Videos

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy05:21

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy

Published on: October 6, 2014

10.0K
A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer06:01

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Published on: July 6, 2017

9.9K

Related Concept Videos

Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.2K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.1K
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...
5.0K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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...
5.8K
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...
5.2K
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...
4.5K