Related Experiment Video

Updated: Aug 8, 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

STAT5 phosphorylation in malignant melanoma is important for survival and is mediated through SRC and JAK1 kinases

Alireza Mirmohammadsadegh1, Mohamad Hassan, Walter Bardenheuer

  • 1Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.

The Journal of Investigative Dermatology
|June 3, 2006
PubMed

Insights

Signal transducer and activator of transcription (STAT)5 is activated in melanoma metastases, promoting tumor growth. Inhibiting STAT5 reduces cell viability and increases apoptosis, suggesting it as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Altered cellular signaling pathways are crucial in tumor development.
  • Signal transducer and activator of transcription (STAT) proteins, particularly STAT3 and STAT5, are implicated in tumor formation and progression.

Purpose of the Study:

  • To investigate the role of STAT5 in cutaneous melanoma metastases.
  • To elucidate the mechanisms of STAT5 activation and its downstream effects in melanoma.

Main Methods:

  • Analysis of Stat5b transcripts and STAT5 phosphorylation in melanoma specimens.
  • Assessment of STAT5 target gene Bcl-2 expression.
  • In vitro studies using recombinant human epidermal growth factor (rEGF) to induce STAT5 activation.
  • Inhibition of Stat5b expression using small interfering RNA (siRNA) and dominant-negative Stat5b transfection.

Main Results:

  • Stat5b transcripts were upregulated approximately 3.8-fold in melanoma.
  • STAT5 was phosphorylated in 62% of human melanoma metastases.
  • The STAT5 target gene Bcl-2 was frequently upregulated.
  • rEGF induced STAT5 activation via src and Janus kinase 1.
  • STAT5 inhibition reduced Bcl-2 expression, decreased cell viability, and increased apoptosis in melanoma cell lines.
  • Dominant-negative Stat5b transfection led to enhanced cell death and G1 arrest.

Conclusions:

  • Phosphorylated STAT5 is present in melanoma and activated by rEGF.
  • STAT5 acts as a survival factor in human melanoma growth.
  • STAT5 represents a potential molecular therapeutic target 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

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