Related Experiment Video

Updated: May 29, 2026

In vitro Organoid Culture of Primary Mouse Colon Tumors
07:33

In vitro Organoid Culture of Primary Mouse Colon Tumors

Published on: May 17, 2013

PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling

R Deevi1, A Fatehullah, I Jagan

  • 1Centre for Cancer Research and Cell Biology, Queen's University of Belfast, Lisburn Road, Belfast BT97BL, UK.

British Journal of Cancer
|September 29, 2011
PubMed
Abstract

Insights

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) influences colorectal cell apoptosis via Cdc42 signaling. PTEN loss reduces Cdc42 activity, inhibiting apoptosis, while PTEN activation enhances it.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The tumor suppressor PTEN regulates epithelial cell polarity via Cdc42 signaling.
  • The precise role of this PTEN-Cdc42 network in regulating apoptosis is not well understood.

Purpose of the Study:

  • To elucidate the function of Cdc42 in PTEN-mediated apoptosis in colorectal cells.
  • To investigate the molecular mechanisms linking PTEN, Cdc42, and programmed cell death.

Main Methods:

  • Utilized isogenic PTEN-expressing and -deficient colorectal cell lines (HCT116, Caco2).
  • Employed flow cytometry, in vitro pull-down assays, and immunoblotting for PARP cleavage analysis.
  • Manipulated Cdc42 activity and PTEN levels using transfection, siRNA, and pharmacological treatments (NaBt, LiCl).

Main Results:

  • PTEN loss or suppression decreased Cdc42 activity, PARP cleavage, and apoptosis.
  • Activated Cdc42 enhanced PARP cleavage and apoptosis; Cdc42 silencing inhibited these processes.
  • PTEN upregulation by NaBt increased Cdc42 activity, PARP cleavage, and apoptosis.
  • Cdc42 signaling suppressed GSK3β activity, and GSK3β inhibition mimicked Cdc42's pro-apoptotic effects.

Conclusions:

  • PTEN signaling modulates apoptosis in colorectal epithelium through the Cdc42 pathway.
  • This pathway integrates regulation of both cell proliferation and programmed cell death.

More Related Videos

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Related Concept Videos

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...
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 daughter...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

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.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...