Related Experiment Video

Updated: Apr 16, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

941

An EGFR/PI3K/AKT axis promotes accumulation of the Rac1-GEF Tiam1 that is critical in EGFR-driven tumorigenesis

G Zhu1,2, Z Fan1, M Ding3

  • 1MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing, China.

Oncogene
|March 10, 2015
PubMed

Insights

Epidermal growth factor receptor (EGFR) signaling activates Rac1 through T-cell lymphoma invasion and metastasis 1 (Tiam1), promoting cancer. This study reveals a bidirectional regulation of Tiam1 stability, crucial for EGFR-driven cancer development.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell signaling

Background:

  • Epidermal growth factor receptor (EGFR) signaling is vital for cell growth and survival.
  • Overactivated EGFR signaling contributes to cancer development.
  • EGFR signaling activates GTPase Rac1, promoting cancer proliferation, survival, and metastasis.

Purpose of the Study:

  • To investigate the mechanism by which EGFR signaling activates Rac1.
  • To elucidate the role of T-cell lymphoma invasion and metastasis 1 (Tiam1) in EGFR-driven cancer.
  • To identify the regulatory mechanisms controlling Tiam1 stability.

Main Methods:

  • Investigated EGFR-induced accumulation of Tiam1 in cancer cells.
  • Analyzed the correlation between Tiam1 and EGFR expression in human cancer specimens.
  • Examined the phosphorylation of Tiam1 by AKT and its interaction with 14-3-3 proteins.
  • Assessed the dephosphorylation and destabilization of Tiam1 by PP2A.

Main Results:

  • EGFR activates Rac1 by inducing Tiam1 accumulation in non-small-cell lung cancer and colon cancer cells.
  • Elevated Tiam1 is essential for EGFR-induced tumorigenesis.
  • Tiam1 expression positively correlates with EGFR expression in lung adenocarcinoma and colon cancer.
  • AKT phosphorylates Tiam1, increasing its stability via 14-3-3 interaction.
  • PP2A dephosphorylates and destabilizes Tiam1.

Conclusions:

  • A bidirectional regulatory mechanism involving phosphorylation and dephosphorylation controls Tiam1 stability.
  • This mechanism provides new insights into EGFR signaling, Rac1 activation, and cancer development.

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
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

9.5K

Related Concept Videos

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...
6.5K
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...
7.6K
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...
5.1K
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:
5.8K
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...
9.5K
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...
8.5K