Related Experiment Video

Updated: May 28, 2026

Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
09:03

Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model

Published on: October 16, 2017

EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation

M Huang1, S Anand, E A Murphy

  • 1Department of Pathology, Moores University of California San Diego Cancer Center, La Jolla, CA 92093-1503, USA.

Oncogene
|October 4, 2011
PubMed

Insights

Epidermal growth factor receptor (EGFR) activates a pathway promoting pancreatic cancer cell invasion and metastasis. This EGFR signaling specifically drives cell migration and spread without affecting primary tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Tyrosine kinase receptors, including epidermal growth factor receptor (EGFR), are crucial in tumor progression.
  • EGFR and its ligands are implicated in the growth and spread of various human carcinomas.

Purpose of the Study:

  • To elucidate an EGFR-mediated signaling pathway regulating human pancreatic carcinoma cell invasion and metastasis.
  • To determine if this pathway affects primary tumor growth.

Main Methods:

  • Investigated EGFR-induced signaling involving Src, p130CAS, Crk-associated substrate (CAS)/Nck1 complex, and Ras-associated protein-1 (Rap1).
  • Assessed the requirement of Rap1 GTP loading for pancreatic carcinoma cell migration on different substrates (vitronectin, collagen).
  • Evaluated the role of Rap1 activation in EGFR-mediated metastasis in vivo.

Main Results:

  • EGFR activation induces Src-dependent phosphorylation of p130CAS, forming a CAS/Nck1 complex that promotes Rap1 signaling.
  • Rap1 activation is essential for pancreatic carcinoma cell migration specifically on vitronectin.
  • EGFR-mediated metastasis in vivo depends on Rap1 activation, independent of primary tumor growth.

Conclusions:

  • Identified a novel EGFR-mediated signaling pathway crucial for pancreatic carcinoma cell invasion and metastasis.
  • This pathway promotes invasive and metastatic properties without influencing primary tumor growth, highlighting a potential therapeutic target.

More Related Videos

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR 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...
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...
MAPK Signaling Cascades01:07

MAPK 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...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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...