Related Experiment Video
Updated: May 11, 2026
09:32
Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Mitogen-activated protein kinase activation regulates intestinal epithelial differentiation
1Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Gastroenterology
|April 30, 1999
Summary
MAP kinase (ERK) activation regulates colon cancer cell differentiation. Inhibiting MEK with PD98059 induced differentiation markers, suggesting ERK signaling is key for goblet cell and enterocyte development.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- The HT29 colon cancer cell line exhibits multipotency.
- A subclone, HT29-18-N2, rich in mucous granules, was utilized to investigate differentiation mechanisms.
Purpose of the Study:
- To determine the cellular mechanisms driving the differentiation of HT29-18-N2 cells.
- To explore the role of mitogen-activated protein (MAP) kinase signaling in this process.
Main Methods:
- Utilized Northern blotting, immunoblotting, and immunocytochemistry on HT29-N2 cells.
- Examined cells under varying glucose conditions and with the MEK inhibitor PD98059.
Main Results:
- Loss of ERK 1/2 activation in glucose-free medium preceded phenotype changes and intestinal trefoil factor (ITF) upregulation.
- MEK inhibition induced terminal differentiation markers (ITF, sucrase-isomaltase, MUC2), gland formation, and mucin secretion.
- Differentiation markers were induced independently of MAP kinase responsiveness loss or receptor tyrosine kinases.
Conclusions:
- ERK activation regulation appears critical for the terminal differentiation of colon crypt-villus unit components.
- This study identifies a key biochemical switch for colonocyte differentiation.
Related Concept Videos
02:38Mitogens 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...
03:03mTOR 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...
The mTOR pathway or the...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:22PI3K/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 rapamycin-insensitive companion...
01:23Renewal of Intestinal Stem Cells
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 goblet,...
01:12Role 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...
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...