Related Experiment Video

Updated: Mar 18, 2026

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells
09:20

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

Published on: July 6, 2021

2.9K

The complexities and versatility of the RAS-to-ERK signalling system in normal and cancer cells

Dirk Fey1, David Matallanas1, Jens Rauch1

  • 1Systems Biology Ireland, UCD School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

Seminars in Cell & Developmental Biology
|June 29, 2016
PubMed

Insights

Understanding the complex RAS-to-ERK signaling network is crucial for effective cancer therapy. Mathematical models are needed to capture its dynamic behavior and improve treatment strategies, moving beyond single-protein inhibition.

Area of Science:

  • Cellular signaling pathways
  • Cancer biology
  • Systems biology

Background:

  • The RAS-to-ERK pathway controls crucial cell functions like proliferation and survival.
  • Current cancer therapies targeting this pathway often show limited efficacy due to complex signaling dynamics.
  • Paradoxical effects, such as ERK activation during RAF inhibition, highlight the need for a deeper understanding.

Purpose of the Study:

  • To review the signaling behavior of RAS and RAF proteins in normal and cancer cells.
  • To discuss the systems-level properties of the RAS-to-ERK signaling network.
  • To advocate for the use of mathematical modeling in understanding this complex pathway.

Main Methods:

  • Literature review of RAS and RAF signaling.
  • Analysis of systems-level properties of the RAS-to-ERK network.
  • Discussion of the role of mathematical modeling in deciphering pathway dynamics.

Main Results:

  • The RAS-to-ERK pathway exhibits intricate dynamic control and plasticity.
  • Single-target inhibition strategies often fail due to the network's context-dependent signaling.
  • Emerging systems-level properties reveal the complexity of signal processing within this network.

Conclusions:

  • A comprehensive understanding of RAS-to-ERK signaling requires considering its dynamic and network properties.
  • Mathematical models incorporating mechanistic details are essential for elucidating pathway complexities.
  • Developing advanced, rational cancer therapies necessitates a foundation built on these dynamic models.
Keywords:
Dynamic modellingMAPK cascadeSystems biology

More Related Videos

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

10.9K
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.4K

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...
5.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.6K
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...
9.1K
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...
7.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.8K
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...
6.2K