Related Experiment Video

Updated: Sep 29, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Roles of activated Src and Stat3 signaling in melanoma tumor cell growth

Guilian Niu1, Tammy Bowman, Mei Huang

  • 1Immunology Program, H Lee Moffitt Cancer Center and Research Institute, Department of Oncology, University of South Florida College of Medicine, Tampa, Florida, FL 33612, USA.

Oncogene
|October 9, 2002
PubMed

Insights

Src tyrosine kinase activation of Stat3 signaling drives melanoma growth and survival. Inhibiting Src or Stat3 induces apoptosis and reduces anti-apoptotic gene expression in melanoma cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Protein tyrosine kinases are frequently activated in cancers, with Stat3 signaling acting as a convergence point.
  • Constitutive Stat3 activation is crucial for tumor cell proliferation and survival in various cancers.
  • Oncogenic signaling pathways in melanoma cells require further elucidation.

Purpose of the Study:

  • To investigate the role of Stat3 signaling in melanoma.
  • To identify the upstream kinases regulating Stat3 activation in melanoma.
  • To determine the impact of inhibiting Src or Stat3 on melanoma cell viability and gene expression.

Main Methods:

  • Assessed Stat3 activation in human melanoma cell lines and tumor specimens.
  • Investigated the effect of blocking Src, EGF receptor, and JAK family kinases on Stat3 signaling.
  • Examined the impact of inhibiting Src kinase activity or Stat3 signaling on melanoma cell apoptosis.
  • Analyzed the expression of anti-apoptotic genes (Bcl-x(L), Mcl-1) following Src or Stat3 blockade.

Main Results:

  • Stat3 is constitutively activated in most examined melanoma cell lines and tumors.
  • Src tyrosine kinase inhibition, but not EGF receptor or JAK inhibition, blocks Stat3 signaling in melanoma.
  • c-Src tyrosine kinase is activated in melanoma cell lines.
  • Inhibition of Src or Stat3 leads to melanoma cell apoptosis.
  • Blockade of Src or Stat3 down-regulates Bcl-x(L) and Mcl-1 gene expression.

Conclusions:

  • Src-activated Stat3 signaling is constitutively active in melanoma.
  • Src-mediated Stat3 activation is essential for melanoma cell growth and survival.
  • Targeting Src or Stat3 signaling represents a potential therapeutic strategy for melanoma.

More Related Videos

A 3D Organotypic Melanoma Spheroid Skin Model08:49

A 3D Organotypic Melanoma Spheroid Skin Model

Published on: May 18, 2018

Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease06:25

Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease

Published on: March 29, 2024

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...
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 JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...