Related Experiment Video

Updated: Jun 19, 2026

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Heregulin-induced VEGF expression via the ErbB3 signaling pathway in colon cancer

Masaoki Yonezawa1, Ken Wada, Atsushi Tatsuguchi

  • 1Division of Gastroenterology, Nippon Medical School, Tokyo, Japan.

Digestion
|October 3, 2009
PubMed
Abstract

Insights

Heregulin (HRG) stimulates vascular endothelial growth factor (VEGF) secretion in colon cancer cells, potentially driving tumor growth. This HRG-VEGF signaling pathway may offer new therapeutic targets for colon cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Heregulin (HRG/NRG) binding to erbB3/4 receptors promotes heterodimerization with erbB2, leading to erbB2 phosphorylation.
  • While HRG is found in various cancers, its specific role in colon cancer remains unclear.

Purpose of the Study:

  • To investigate the expression of erbB receptors, HRG, and vascular endothelial growth factor (VEGF) in colon cancer.
  • To determine the relationship between HRG and VEGF expression and signaling in colon cancer.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) and Western blot were used to analyze HRG effects on VEGF secretion and signaling pathways (PI-3K, Akt, ERK1/2, p38 MAPK) in colorectal cancer cell lines.
  • Real-time PCR and immunohistochemistry were employed to assess HRG and VEGF mRNA and protein expression in colon cancer biopsy samples.

Main Results:

  • Exogenous HRG significantly increased VEGF secretion and mRNA expression in colon cancer cell lines.
  • HRG activated key signaling molecules including p85 PI-3K, Akt, ERK1/2, and p38 MAPK.
  • HRG mRNA expression positively correlated with VEGF mRNA expression in colon cancer tissues, with HRG protein detected in both cancer and mesenchymal cells.

Conclusions:

  • HRG regulates VEGF secretion through the erbB3 signaling pathway, potentially impacting colon cancer growth via autocrine and paracrine mechanisms.
  • The HRG-VEGF axis represents a potential therapeutic target for colon cancer.

More Related Videos

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors09:04

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors

Published on: March 15, 2016

Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia07:48

Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia

Published on: June 8, 2019

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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.
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Mitogens and the Cell Cycle02:38

Mitogens 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...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...