Increased cytokine secretion in head and neck cancer upon p38 mitogen-activated protein kinase activation

Christine Riebe1, Ralph Pries, Andrea Kemkers

  • 1Department of Otorhinolaryngology, University of Schleswig-Holstein Campus Lübeck, 23538 Lübeck, Germany.

Insights

Head and neck squamous cell carcinoma (HNSCC) involves impaired immune function. This study shows that activating MAP (mitogen-activated protein) kinase p38 in HNSCC decreases cell proliferation and increases IL-6 and IL-8 cytokine secretion.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer associated with suppressed immune functions.
  • The specific signal transduction pathways driving immune suppression in HNSCC remain largely unidentified.

Purpose of the Study:

  • To investigate the role of MAP (mitogen-activated protein) kinase p38 signaling in HNSCC.
  • To elucidate the impact of p38 activation on HNSCC cell behavior and cytokine secretion.

Main Methods:

  • Analysis of MAP kinase p38 phosphorylation levels in HNSCC cell lines and tumor tissues via flow cytometry and SDS-PAGE.
  • Quantification of cytokine secretion (IL-6, IL-8) using the Cytometric Bead Array Flex Set system.
  • Induction of p38 activation using phorbol 12-myristate 13-acetate.

Main Results:

  • MAP kinase p38 was activated in HNSCC models.
  • p38 activation led to reduced HNSCC cell proliferation.
  • Increased secretion of cytokines IL-6 and IL-8 was observed following p38 activation.

Conclusions:

  • MAP kinase p38 signaling plays a significant role in modulating the HNSCC microenvironment.
  • Understanding these molecular mechanisms offers potential for new therapeutic strategies and improved clinical outcomes for HNSCC patients.

Related Concept Videos

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...
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...
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 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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
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...