Related Experiment Video
Updated: Nov 11, 2025
06:40
3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation
Published on: April 1, 2021
5.1K
LIN28B induces a differentiation program through CDX2 in colon cancer.
Kensuke Suzuki1, Yasunori Masuike1, Rei Mizuno2
1Herbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Disease, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA.
JCI Insight
|March 23, 2021
Summary
The LIN28B/CDX2 signaling axis promotes colorectal cancer (CRC) differentiation. LIN28B enhances CDX2 expression, which upregulates AMACR, a key factor in intestinal differentiation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Most colorectal cancers (CRCs) maintain moderate or well-differentiated status, even in metastatic stages.
- The precise molecular mechanisms governing CRC differentiation remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying colorectal cancer differentiation.
- To investigate the role of the LIN28B/CDX2 signaling axis in mediating CRC differentiation.
Main Methods:
- RNA-binding protein immunoprecipitation (RIP) assay to identify direct interactions between LIN28B and CDX2 mRNA.
- Xenograft and mouse models of CRC liver metastasis to assess the in vivo effects of LIN28B overexpression.
- Chromatin immunoprecipitation sequencing (ChIP-seq) to identify CDX2 transcriptional targets.
Main Results:
- LIN28B directly binds and enhances CDX2 mRNA expression, promoting CRC cell differentiation.
- LIN28B overexpression promotes differentiation in xenograft tumors and inhibits metastasis in mouse models.
- CDX2, regulated by LIN28B, targets AMACR, which enhances intestinal alkaline phosphatase activity via butyric acid.
Conclusions:
- LIN28B acts as a key regulator of CRC differentiation through the CDX2/AMACR signaling pathway.
- This pathway represents a potential therapeutic target for modulating CRC differentiation and progression.
Related Concept Videos
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.2K
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...
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
01:23Renewal of Intestinal Stem Cells
2.9K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
2.9K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.4K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.4K
02:54Canonical Wnt Signaling Pathway
9.5K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
9.5K
02:23Abnormal Proliferation
4.8K
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...
4.8K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
8.5K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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...
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...
8.5K