Adenosine diphosphate-ribosylation factor 6 is required for epidermal growth factor-induced glioblastoma cell

Ming Li1, Jide Wang, Samuel S M Ng

  • 1Department of Chemistry, Open Laboratory of Chemical Biology, the University of Hong Kong, Hong Kong, China.

Cancer
|July 31, 2009
PubMed
Abstract

Insights

Epidermal growth factor (EGF) stimulates adenosine diphosphate-ribosylation factor 6 (ARF6) expression in glioblastoma cells, promoting proliferation. This EGF-induced ARF6 upregulation is crucial for glioblastoma cell growth, highlighting a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Epidermal growth factor (EGF) signaling is critical in gliomagenesis.
  • Adenosine diphosphate-ribosylation factor 6 (ARF6) is implicated in glioma cell migration and invasion.
  • The precise role of ARF6 in EGF signaling within gliomas remains unclear.

Purpose of the Study:

  • To investigate the role of ARF6 in EGF signaling pathways in glioma.
  • To determine if EGF influences ARF6 expression in glioblastoma cells.
  • To elucidate the downstream signaling mechanisms and functional consequences of EGF-induced ARF6 expression.

Main Methods:

  • Analyzed ARF6 and EGFR mRNA levels in glioma tissues using RT-PCR.
  • Assayed ARF6 expression in U87 cells following EGF stimulation, with and without inhibitors of transcription and EGFR.
  • Investigated downstream signaling pathways (MEK/ERK, PI3K) and SP1 involvement.
  • Utilized small-interfering RNAs (siRNAs) to assess ARF6's effect on EGF-mediated cell proliferation.

Main Results:

  • Elevated ARF6 and EGFR mRNA levels were observed in glioma tissues.
  • EGF dose- and time-dependently increased ARF6 expression via transcriptional regulation.
  • EGF-induced ARF6 upregulation involved MEK/ERK and PI3K signaling pathways and was dependent on SP1.
  • Suppression of ARF6 significantly inhibited EGF-induced glioblastoma cell proliferation.

Conclusions:

  • EGF-induced ARF6 expression plays a significant role in glioma cell proliferation.
  • ARF6 is a key mediator of EGF signaling in glioblastoma.
  • Targeting the EGF-ARF6 axis may offer a therapeutic strategy for glioma.

Related Concept Videos

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...
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...
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...
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...
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...