Related Experiment Video

Updated: Nov 12, 2025

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
12:37

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model

Published on: September 7, 2013

18.5K

EGR-1 plays a protective role in AMPK inhibitor compound C-induced apoptosis through ROS-induced ERK activation in

Kai-Cheng Chuang1, Fan-Wen Chen1, Meng-Hsiun Tsai2,3

  • 1Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan, R.O.C.

Oncology Letters
|March 18, 2021
PubMed

Insights

Compound C induces skin cancer cell death via a novel pathway involving early growth response-1 (EGR-1) and extracellular signal-regulated kinase (ERK) activation. EGR-1 antagonizes apoptosis but not autophagy, offering new therapeutic targets for skin cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Skin cancer arises from uncontrolled epidermal cell growth, mutation, and gene dysregulation.
  • Compound C, an AMP-activated protein kinase (AMPK) inhibitor, induces apoptosis and autophagy in skin cancer cells through AMPK-independent mechanisms.
  • The precise signaling pathways triggered by Compound C in cancer cells remain largely unknown.

Purpose of the Study:

  • To elucidate the signaling pathways activated by Compound C in skin cancer cells.
  • To investigate the role of early growth response-1 (EGR-1) in Compound C-induced cell death.
  • To determine the relationship between EGR-1, reactive oxygen species (ROS), and extracellular signal-regulated kinase (ERK) signaling.

Main Methods:

  • Oligodeoxynucleotide-based microarray screening to identify differentially expressed genes.
  • Quantitative real-time PCR and Western blotting to assess mRNA and protein expression.
  • Confocal microscopy for protein localization, and functional assays including gene knockdown and reactive oxygen species scavenging.

Main Results:

  • Compound C significantly upregulated early growth response-1 (EGR-1) mRNA and protein in a time- and dose-dependent manner, with nuclear localization.
  • Compound C activated extracellular signal-regulated kinase (ERK) phosphorylation; inhibiting ERK or scavenging reactive oxygen species (ROS) reduced EGR-1 expression.
  • EGR-1 knockdown in cancer cells decreased survival and increased caspase-3 activity and apoptosis markers post-Compound C treatment, but did not affect autophagy markers.

Conclusions:

  • Early growth response-1 (EGR-1) antagonizes Compound C-induced apoptosis in skin cancer cells.
  • This antagonism is mediated through a pathway involving reactive oxygen species (ROS) and extracellular signal-regulated kinase (ERK) activation.
  • EGR-1 does not appear to influence Compound C-induced autophagy, suggesting distinct roles in Compound C's cytotoxic effects.
Keywords:
adenosine 5′ monophosphate-activated protein kinasecompound Cearly growth response-1

More Related Videos

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells09:20

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

Published on: July 6, 2021

2.6K
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.2K

Related Concept Videos

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...
7.0K
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...
7.3K
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...
4.5K
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...
4.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.3K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
82.4K