TSR2 Induces laryngeal cancer cell apoptosis through inhibiting NF-κB signaling pathway

Hong-Jiang He1, Han Bing2, Guijun Liu3

  • 1Department of Head and Neck Surgery, Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.

The Laryngoscope
|December 28, 2017
PubMed
Abstract

Insights

TSR2 is downregulated in laryngeal squamous cell carcinoma (LSCC). Overexpressing TSR2 promotes LSCC cell apoptosis by inhibiting the NF-κB signaling pathway, offering a potential gene therapy target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Human laryngeal squamous cell carcinoma (LSCC) is a malignancy originating in the laryngeal mucosa epithelium.
  • The precise molecular mechanisms driving LSCC progression remain unclear.
  • Investigating novel molecular targets is crucial for developing effective LSCC therapies.

Purpose of the Study:

  • To elucidate the role of TSR2 in LSCC.
  • To investigate the molecular mechanisms by which TSR2 influences LSCC cell apoptosis.
  • To explore TSR2 as a potential therapeutic target for LSCC.

Main Methods:

  • Quantitative real-time polymerase chain reaction (qRT-PCR) to assess TSR2 expression in LSCC tissues and cells.
  • Overexpression of TSR2 in LSCC cell lines (Hep-2 and AMC-HN-8) using pcDNA3.1-TSR2.
  • Western blot and terminal dUTP nick end-labeling assays to evaluate apoptosis-related proteins and NF-κB p65 nuclear translocation.

Main Results:

  • TSR2 was found to be significantly downregulated in LSCC tissues and cells compared to normal controls.
  • Overexpression of TSR2 promoted apoptosis in LSCC cells and upregulated apoptosis-related proteins.
  • TSR2 overexpression inhibited the NF-κB signaling pathway by reducing nuclear NF-κB p65 and increasing cytoplasmic NF-κB p65, while also inhibiting IκBα and IKKα/β phosphorylation.

Conclusions:

  • TSR2 plays a suppressive role in LSCC development.
  • TSR2-induced apoptosis in LSCC is mediated through the inhibition of the NF-κB signaling pathway.
  • TSR2 represents a promising molecular target for gene therapy in LSCC treatment.

Related Concept Videos

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...
10.1K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.6K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.2K
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...
7.4K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.5K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.7K