Related Experiment Video

Updated: Jun 1, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

A novel role of dipeptidyl peptidase 9 in epidermal growth factor signaling

Tsun-Wen Yao1, Woo-Shin Kim, Denise M T Yu

  • 1Centenary Institute, University of Sydney, NSW, Australia.

Molecular Cancer Research : MCR
|May 31, 2011
PubMed

Insights

Dipeptidyl peptidase 9 (DPP9) inhibits Akt pathway activation, impacting cell survival and proliferation. This novel role involves interaction with H-Ras, suggesting DPP9

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Dipeptidyl peptidase IV (DPP4) family proteases, including DPP8, DPP9, and fibroblast activation protein (FAP), exhibit diverse enzymatic and extra-enzymatic functions.
  • These proteases are implicated in the pathogenesis of various diseases, notably cancers.

Purpose of the Study:

  • To elucidate the novel role of Dipeptidyl peptidase 9 (DPP9) in regulating cell survival and proliferation.
  • To investigate the molecular signaling cascades modulated by DPP9, particularly its effect on the Akt pathway.

Main Methods:

  • Overexpression of human DPP9 in human hepatoma (HepG2, Huh7) and embryonic kidney (HEK293T) cells.
  • Assessing Akt (protein kinase B) and extracellular signal-regulated kinases (ERK1/2) activation.
  • Investigating growth factor dependency (EGF, CTGF, HGF, insulin, PDGF-BB) of DPP9's effects.
  • Enzyme activity ablation via mutagenesis and inhibition.
  • Co-immunoprecipitation assays to determine interactions with H-Ras.

Main Results:

  • DPP9 overexpression significantly inhibited Akt activation in a pathway-specific manner, without affecting ERK1/2.
  • The inhibitory effect on Akt was dependent on epidermal growth factor (EGF) stimulation and led to increased apoptosis.
  • DPP9 and DPP8, but not DPP4 or FAP, were found to associate with H-Ras, a critical component of the EGF receptor signaling pathway.
  • DPP9's inhibitory effect on Akt was dependent on its enzymatic activity.

Conclusions:

  • DPP9 plays a significant role in regulating cell survival and proliferation by modulating the PI3K/Akt signaling pathway.
  • DPP9's interaction with H-Ras suggests a mechanism for its influence on EGF receptor-mediated signaling.
  • These findings highlight DPP9 as a potential therapeutic target in diseases involving dysregulated cell signaling.

More Related Videos

Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells08:28

Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells

Published on: May 9, 2025

Related Concept Videos

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.
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...
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...
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...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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 rapamycin-insensitive companion...