HPRT promotes proliferation and metastasis in head and neck squamous cell carcinoma through direct interaction with

Lin Wang1, Yupu Wang1, Nannan Han1

  • 1Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China; National Clinical Research Center for Oral Disease, Shanghai, 200011, China.

Experimental Cell Research
|December 19, 2020
PubMed

Insights

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) promotes head and neck squamous cell cancer (HNSCC) progression by interacting with STAT3. Reducing HPRT enhances EGFR inhibitor efficacy, suggesting HPRT as a therapeutic target for HNSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Head and neck squamous cell cancer (HNSCC) requires novel therapeutic strategies.
  • Improving the efficacy of Epidermal Growth Factor Receptor (EGFR) inhibitors is a key challenge.

Purpose of the Study:

  • To investigate the role of Hypoxanthine-guanine phosphoribosyltransferase (HPRT) in HNSCC.
  • To identify HPRT as a potential therapeutic target and prognostic indicator for HNSCC.

Main Methods:

  • Bioinformatic analysis of The Cancer Genome Atlas (TCGA) RNA-Seq data.
  • In vitro and in vivo loss- and gain-of-function experiments in HNSCC cell lines and xenografts.
  • Investigation of HPRT's interaction with Signal Transducer and Activator of Transcription 3 (STAT3).

Main Results:

  • Higher HPRT expression in HNSCC tissues correlates with poor patient prognosis.
  • HPRT overexpression promotes epithelial-mesenchymal transition (EMT) markers via STAT3 interaction.
  • HPRT knockdown reduces tumor growth and sensitizes HNSCC to EGFR inhibitors.

Conclusions:

  • HPRT acts as a STAT3 binding partner, promoting EMT and proliferation in HNSCC.
  • HPRT is a potential prognostic biomarker and therapeutic target for HNSCC treatment.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.9K
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...
4.1K
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...
4.8K
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...
6.9K
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...
7.4K
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...
10.5K